Unlocking Zinc’s Potential to Fight Cancer

Background:

When I first dived into the supplements that could help fight cancer, one of those I came across was Zinc. I found a lot of literature indicating that Zinc would indeed represent an useful tool, but also found literature indicating that cancer cells may actually like Zinc. In line with this, there are holistic doctors and naturophats who are recommending the use of Zinc to their cancer patients, while others are totally against that. As a result, although I ordered some bottles of capsules, I decided not to use them. There are so many potential treatments out there, and it would not make sense to use something as long as we do not understand it and its potential is still debated.

However, latter I did a deeper dive into this subject to better understand it and as a result of that I became enthusiastic regarding the potential of Zinc in cancer. As I will further discuss, based on my current understanding taking Zinc alone will not help. But when combined with another drug, Zinc may have a great potential.

Speaking about the potential of Zinc in cancer, a very recent (2017) scientific review from Department of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, MD, USA, was stating the following: “The absence of the essential and correct understanding of the zinc relationships has resulted in unfounded and misguided criticisms and objections regarding the status and implications of zinc in cancer.” (Ref.) If you want to better understand the relevance of Zinc in cancers, I highly recommend to read the review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183570/

As the review above explains, the misguiding of this field was related to the fact that some scientists were suggesting Zinc actually helps the development of cancer cells, since its depletion in some experiments would stop the development. An example of such study is here (Ref.). Yet, as clarified in another paper (Ref.) and in the review above, these kind of studies may be misleading since they are not representing the status and behavior of cells in the human body, in tissue, but represent extreme conditions only possible in the lab.

When searching the literature, what we will find is that most cancer cells maintain their level of Zinc lower then normal cells (for example prostate cancer, liver cancer (Ref.1, Ref.2), pancreatic cancer (Ref.), etc.), with the exception of breast cancer where it seems to be increased compared to normal cells. As we will see in some of the references below, regardless of the normal level of Zinc in cancer cells, when we push more Zinc than they actually need (Ref.), there is a good chance the cancer cells will be killed. From a cancer development point of view, note that Zinc deficiency is believed to be one road towards getting cancer, typical in developed countries (Ref.).

The Zinc level in most of cancer cells seems to be maintained via a down regulation of the (ZIP) transporters responsible for the transport of Zinc across cellular membrane (Ref.). That means, that we can take as much Zinc supplements as we like, and yet that may never get into the cancer cells at the level required to disrupt their normal function.

So what can we do, if we want to push more Zinc into the cancer cells and disrupt their function?

Fortunately, there is a group of chemicals that are called Zinc ionophores (Ref.). Those chemicals have the capability to bind and transport Zinc inside the cancer cell, even if the Zinc transporters are down regulated in cancer cells. Once inside the cancer cell at a level high enough, it has the potential to stop cell functions, regardless of whether we speak about e.g. prostate cancer, etc. with a low level of zinc or e.g. breast cancer with a high level of zinc, prior to Zinc treatment. And the good news is that Zinc ionophores are widely available, used to treat other human problems, while they are also known for their anti cancer action – even when not using Zinc supplementation. Yet, Zinc supplementation is expected to enhance their action.

Disulfiram is one such Zinc ionophore drug, commonly used as an anti alcohol drug with a long track record of safety in humans (Ref.). As discussed in a previous article (see here) Chloroquine (Ref.) and Clioquinole, both widely available drugs for oral or topical admin., are also Zinc ionophores. Ethambutol, a drug used to treat tuberculosis is also a Zinc ionophore (Ref.1, Ref.2). I will mainly discuss Disulfiram in the following since its effectivenss is already proven, but other Zn ionophores can be considered as well.

As a side remark, combinations of Zinc and another Zinc ionophore called Pyrithione have a long history of use in shampoos to treat dandruff and seborrhoeic dermatitis and is known to exhibit both antifungaland antimicrobial properties. It can be used as an antibacterial agent against Staphylococcus and Streptococcus infections for conditions such as athlete’s foot, eczema, psoriasis, and ringworm. All the relevant references are in this article on Wikipedia (Ref.).

Here are some studies where Zinc alone or in combination with Zinc ionophores has been shown effective in killing cancer cells in the lab:

  • Breast cancer (Ref.) Here is a recent PhD thesis discussing the combination of Disulfiram and Zn in breast cancer as an anticancer approach: Investigation into the effects of zinc on the anti-breast cancer properties of disulfiram https://orca.cf.ac.uk/87744/1/2016WigginsHPhD.pdf
    In another study (Ref.), intracellular Zinc accumulation was shown to support Tamoxifen anti cancer activity.
  • Melanoma (Ref.) On melanoma there are multiple case reports published. Please see them below.
  • Hepatocellular cancer HCC (Ref.) The reference also discussing the relevance of Zinc supplementation to improve the outcome of patients with chronic hepatitis C (Ref.) And here is an article representing a collaboration between a large number of institutions suggesting that Zinc may indeed have a role in preventing liver-cancer development (Ref.)
  • Pancreatic cancer (Ref.)
  • Prostate cancer (Ref.1, Ref.2, Ref.3, Ref.4)
  • Colon cancer (Ref. 1, Ref.2)
  • Esophageal cancer (Ref.1, Ref.2)

Other benefits of Zinc:

  • enhances the immune system (Ref.1, Ref.2, Ref.3, Ref.4)
  • offers protection to patients older than 70 years against the cognitive decline (in Alzheimer’s disease) by decreasing the levels of free copper (Ref.).
  • improvement of symptoms in patients suffering from depression (Ref.).
  • decreasing the risk of incidence of ocular diseases correlated to aging (Ref.)
  • decreasing the incidence of infections in the elderly (Ref.) and anemia patients (Ref.).
  • positive impact on fertility (Ref.)

Food containing high level of Zinc: Oysters, Beef, Lamb, Venison, Sesame seeds, Pumpkin seeds, Yogurt, Turkey, Green peas, Shrimp.

Successful case reports on Zinc + Disulfiram in Humans

  • Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. https://www.ncbi.nlm.nih.gov/pubmed/15367699
    http://mct.aacrjournals.org/content/3/9/1049
    Here is a quote from the article “We also report the first use of disulfiram and Zn2+ to treat advanced stage IV metastatic melanoma in a patient. This was done with approval from the Carolinas Medical Center Institutional Review Board, informed consent was obtained, data were collected prospectively, and the patient has been on no other treatment for melanoma. The subject treated is a 64-year-old woman who presented with a nonoperable central liver metastasis from a T2 ocular melanoma that had been removed 5 years previously. She had developed abdominal pain and was found to have a 2.3 cm right hepatic metastasis and a 5.5 cm central liver metastasis confirmed as recurrent melanoma by biopsy. She declined chemotherapy, interleukin-2 therapy, or liver perfusion. After granting informed consent, she was started on 250 mg/d disulfiram (Antabuse, Wyeth, Madison, NJ) with the largest meal of the day. This dose was increased to 500 mg/d after 1 month. Zinc gluconate (50 mg chelated elemental Zn2+, General Nutrition Center, San Francisco, CA) was also given thrice daily but not concurrent with disulfiram administration. This heavy metal and its dose were chosen for previously demonstrated safety in humans as the preventative treatment for Wilson’s disease. Doses of each agent were those currently recommended for treatment of alcoholism and Wilson’s disease, respectively. On starting the protocol, the patient suffered grade 1 (National Cancer Institute Common Toxicity Criteria, version 2.0) diarrhea, nausea, depression, and malaise. Except for nausea, these side effects resolved within 2 months of continued treatment. Her abdominal pain also completely resolved and she returned to work. After 9 months, disulfiram was reduced to 250 mg/d and her nausea ceased. She has continued on disulfiram 250 mg/d and zinc gluconate 50 mg thrice daily. All laboratory studies have remained normal. Repeat computed tomography and positron emission tomography scans after 3 months of therapy showed a >50% reduction in tumor size (Fig. 10, top). A positron emission tomography scan 12 months after initiating treatment showed the lesions to be stable (Fig. 10, bottom), and the most recent computed tomography scan after 42 months of treatment (Fig. 10, top, far right) shows that residual hepatic disease has remained stable. She continues to be clinically well and physically active after 53 continuous months of therapy.”

And here is a Fig. from the article showing the tumor shrinkage:

  • Another case report was presented in the patent: Method of inhibiting ATF/CREB and cancer cell growth and pharmaceutical compositions for same https://www.google.com/patents/US20040019102
    Here is a quote from the patent: “a 57 year old woman who had a Clark Level III, 0.73 mm thick melanoma excised from her left back 9 years prior to entering the study. Patient #3 received no adjuvant treatment and developed a left axillary metastasis 4 years later, treated by axillary dissection. The patient received a year of adjuvant alpha interferon and 8 months later was found to have a chest wall and a lung metastasis. The patient was treated with high dose interleukin-2 but then developed additional axillary metastases requiring further dissection and radiation. Patient #3 refused standard chemotherapy. When beginning disulfiram and zinc gluconate, the patient had metastatic disease to the pelvic lymph nodes, left lung, and multiple subcutaneous sites. Initially, patient #3 suffered grade 1 diarrhea, fatigue, malaise, increased anxiety and depression. Diarrhea and malaise completely resolved within 2 months. Anxiety and depression were controlled with medication. Laboratory studies remained normal. Patient #3 temporarily stopped treatment for 5 weeks so that the patient could consume alcohol at a wedding, but resumed treatment at 250 mg disulfiram daily and 50 mg zinc gluconate three times daily and remained clinically stable and free of tumor progression 12 months after first initiating therapy. Interval PET scans showed no new lesions, 3 lung and lymph node mestastases that are stable, resolution of an area of soft tissue metastasis at the right iliac crest, and development of central necrosis in an area of soft tissue metastasis in the posterior left shoulder.”
    .
  • Here is the website of a Russian medical doctor and PhD (Dr. Jacob L. Turumin), presenting several cases of successful treatment of melanoma patients, using Disulfiram + Zn + Cu: http://www.drturumin.com/en/Melanoma_en.html
    The website includes very clear pictures showing tumor shirinkage after using such treatment in oral and or topical form. He finally concludes that “This algorithm of the pathogenetic treatment may help to decrease mortality and may help to increase a survival of patients with melanoma. Probably it will help to raise the 5 years survival rate up to 50 % in the patients with secondary metastatic melanoma.”

Patent on Disulfiram + Zinc:

Method of inhibiting ATF/CREB and cancer cell growth and pharmaceutical compositions for same  (Ref.)

There is provided a method for inhibiting ATF/CREB and cancer cell growth using disulfiram, administered in combination with heavy metals. It was found that disulfiram disrupts transcription factor DNA binding by forming mixed disulfides with thiols within the DNA-binding region, and that this process is facilitated by metal ions. Disulfiram administered to melanoma cells in combination with copper (II) or zinc(II) decreased expression of cyclin A, reduced proliferation in vitro, and inhibited growth of melanoma cells. The combination of oral zinc gluconate and disulfiram at currently approved doses for alcoholism stabilized tumor growth in two of three patients with Stage IV metastatic melanoma, with 12 and 17 month survivals, respectively, to date, and produced a >50% reduction in hepatic metastases in one individual.

Although not including Zinc, but nice to mention, here is a patent on Disulfiram for Breast Cancer:

Use of Disulfiram for Inflammatory Breast Cancer Therapy  (Ref.)

Methods, compositions of matter, and kits for treatment of breast cancer, and in particular for inflammatory breast cancer, in a patient are disclosed. The methods can include administering a redox modulating agent to the patient. The redox modulating agent can be disulfiram.

Mechanism

Increasing Reactive Oxygen Species (Ref.) therefore not best to combine with strong anti oxidants.

Enhances the immune system (Ref.1, Ref.2, Ref.3, Ref.4)

Another mechanism related to Zn anti-cancer activity was recently found to be connected to the fact that zinc impedes overactive calcium signals in cancer cells, which is absent in normal cells (Ref.1, Ref.2) Interestingly, many anti cancer substances are interfering with intra cellular calcium activity, as I previously discussed here.

For more details on the mechanism please read the enclosed references.

Application:

Oral application according to Brar’s paper (Ref.):

  • 250 mg/d disulfiram (Antabuse, Wyeth, Madison, NJ) with the largest meal of the day. This dose was increased to 500 mg/d after 1 month.
  • Zinc gluconate (50 mg chelated elemental Zn2+,) was also given thrice daily but not concurrent with disulfiram administration.

Oral and topical application according to Dr. Jacob L. Turumin website (this was suggested for melanoma but it can be considered for other cancer types as well):

  • Before operation: During 2-4 weeks a patient receives a local treatment (disulfiram plus CuSO4 – drops) and systemic treatment (disulfiram plus ZnSO4 – tablets) for decrease of melanoma cells activity.
  • Immediately after the operation a patient receives a local treatment (if possible Esperal which is a sterile form of disulfiram tablets) for a future decrease of melanoma cells activity and formation of local relapse.
  • After operation during 1-6 months (maximal period may make up 5 years) a patient can receive a partial local pathogenetic treatment (disulfiram plus CuSO4 – drops) and/or a systemic pathogenetic treatment (disulfiram plus ZnSO4 – tablets) for decrease of risk of melanoma metastases.
  • Doses used were  disulfiram (500 mg/day) plus zinc sulfate (ZnSO4 – 45 to 90 mg chelated elemental Zn2+ – thrice daily) – essentially same as above

Note: During the Disulfiram usage, the patient needs to stop alcohol usage as side effects will be triggered, since it is used to support detox for alcohol dependence. That is a drawback since no other medication that contains alcohol can be used. Note that some IV treatments (including Curcumin) may contain ethanol.

Better to avoid combining Zinc with Selenium (Ref.)

As prevention we can use 15-30mg Zinc/day with food.

Safety:

It is known to be a drug with moderate side-effects.  Significant side-effects include hepatitis (1 case in 30,000 treated/yr), and neurologic. Rare reports of psychosis and confusional states. Tiredness, headache and sleepiness are the most common. The metabolism of other drugs may be inhibited by disulfiram, increasing their potential for toxic effects.

Drugs known to have adverse effects when used concurrently with disulfiram include amitriptyline, isoniazid, and metronidazole (all with acute changes in mental state), phenytoin, some benzodiazepines, morphine, pethidine, and barbiturates.

Source:

Disulfiram (at the pharmacy) and Zinc (at the supplement store)  are widely available, are cheap so should be accessible to anyone.

Update 23-09-2019: Due to this reason (Ref.), it’s best to use Zinc Gluconate.

Other references:

Direct Effect of Zinc on Mitochondrial Apoptogenesis in Prostate Cells https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465826/

Exposure to zinc induces apoptosis in PC-3 and BPH cells, which accumulate high intracellular levels of zinc, but not in HPR-1 cells, which do not accumulate high levels of zinc. Once initiated, the induction of apoptosis is not reversed by the removal of zinc, i.e., it is an irreversible process. The apoptogenic effect is due to a direct effect of zinc on mitochondria that results in the release of cytochrome c. The cell specificity of zinc induction of apoptogenesis is dependent on the ability of the cells to accumulate high levels of intracellular zinc and on the ability of the mitochondria to respond to the direct effect of zinc.

The Metabolic Phenotype of Prostate Cancer https://www.ncbi.nlm.nih.gov/pubmed/28674679

Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. https://www.ncbi.nlm.nih.gov/pubmed/9609552

The prostate gland of humans and many other animals has the major function of accumulating and secreting extraordinarily high levels of citrate. This specialized metabolic process of “net citrate production” is the result of unique metabolic capabilities of the secretory epithelial cells. Most importantly, in prostate cancer (Pca) the capability for net citrate production is lost. In addition to citrate, the normal and BPH (benign prostatic hyperplasia) prostate also accumulates the highest levels of zinc in the body. As with citrate, in Pca the ability for high zincaccumulation is diminished. These and other correlations between zinc and citrate in the prostate have been indicative of an important role of zinc in the regulation of citrate metabolism in normal and malignant prostate epithelial cells. The link between zinc and citrate metabolism has now been established. The intramitochondrial accumulation of high zinc levels inhibits mitochondrial (m-) aconitase activity, which inhibits citrate oxidation. This essentially truncates the Krebs cycle and markedly decreases the cellular energy (ATP) production normally coupled to citrate oxidation. It is also clear that zinc accumulation in citrate-producing prostate epithelial cells is regulated by testosterone and by prolactin. These relationships form the basis for a new concept of the role of zinc and citrate-related energy metabolism in prostatemalignancy. The inability of malignant prostate cells to accumulate high zinc levels results in increased citrate oxidation and the coupled ATP production essential for the progression of malignancy. The concept offers new approaches to the treatment of Pca.

Metal Ionophores – An Emerging Class of Anticancer Drugs http://onlinelibrary.wiley.com/doi/10.1002/iub.253/pdf

Compounds that bind metals such as copper and zinc have many biological activities, including the ability to induce apoptosis in cancer cells. Although some of these compounds have been considered to act as chelators of metals, decreasing their bioavailability, others increase intracellular metal concentrations. We review recent work regarding the recognition of the biological effects of metal ionophores with different structures, particularly with regard to their actions upon cancer cells
focusing on dithiocarbamates, pyrithione, and the 8-hydroxyquinoline derivative, clioquinol. We provide a biologically based
classification of metal-binding compounds that allows an experimental distinction between chelators and ionophores that can be readily used by biologists, which may lead to further study and classification of metal-binding drugs. Metal ionophores may kill cancer cells by a number of mechanisms, including lysosomal disruption and proteasome inhibition, and likely others. Because some of these compounds have been safely administered to animals and humans, they have the potential to become clinically useful anticancer agents

Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model. https://www.ncbi.nlm.nih.gov/pubmed/25050823

The status of zinc in the development of hepatocellular cancer: An important, but neglected, clinically established relationship https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979811/#R54

Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75% of HCC cases result in death generally within one year. The factors responsible for the initiation and progression of HCC remain largely unknown and speculative, thereby impeding advancements in the development of effective therapeutic agents and biomarkers for early detection of HCC. A consistent marked decrease in zinc in HCC tumors compared with normal liver is an established clinical relationship, which occurs in virtually all cases of HCC. However, this relationship has been largely ignored by the contemporary clinical and research community. Consequently, the factors and mechanisms involved in this relationship have not been addressed. Thus, the opportunity and potential for its employment as biomarkers for early identification of malignancy, and for development of a chemotherapeutic approach have been lacking. This presentation includes a review of the literature and the description of important recent and new data, which provide the basis for a concept of the role of zinc in the development of HCC. The basis is presented for characterizing HCC malignancy as ZIP14-deficient tumors, and its requirement to prevent zinc cytotoxic effects on the malignant cells. The potential for an efficacious zinc treatment approach for HCC is described. The involvement of zinc in the predisposition for HCC by chronic liver disease/cirrhosis is presented. Hopefully, this presentation will raise the awareness, interest, and support for the much needed research in the implications of zinc in the development and progression of HCC.

Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma. https://www.ncbi.nlm.nih.gov/pubmed/21613827

This report provides the clinical foundation for further mechanistic studies that will provide important insight into pancreatic carcinogenesis, and can lead to the development of effective early biomarkers and effective therapeutic agents for pancreatic cancer.

Zinc transporters and dysregulated channels in cancers https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199720/

As a nutritionally essential metal ion, zinc (Zn) not only constitutes a structural element for more than 3000 proteins but also plays important regulatory functions in cellular signal transduction. Zn homeostasis is tightly controlled by regulating the flux of Zn across cell membranes through specific transporters, i.e. ZnT and ZIP family proteins. Zn deficiency and malfunction of Zn transporters have been associated with many chronic diseases including cancer. However, the mechanisms underlying Zn regulatory functions in cellular signaling and their impact on the pathogenesis and progression of cancers remain largely unknown. In addition to these acknowledged multifunctions, Zn modulates a wide range of ion channels that in turn may also play an important role in cancer biology. The goal of this review is to propose how zinc deficiency, through modified Zn homeostasis, transporter activity and the putative regulatory function of Zn can influence ion channel activity, and thereby contribute to carcinogenesis and tumorigenesis. This review intends to stimulate interest in, and support for research into the understanding of Zn-modulated channels in cancers, and to search for novel biomarkers facilitating effective clinical stratification of high risk cancer patients as well as improved prevention and therapy in this emerging field.

The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots https://www.ncbi.nlm.nih.gov/pubmed/16700911

The genetic/metabolic relationships in normal prostate glandular epithelium are driven by the unique function to accumulate and secrete citrate. The genetic/metabolic transformation of the prostate malignant cells is driven by the metabolic/bioenergetic, growth/proliferative, and invasive/migration requirements of the malignant process. Zinc is critical to these relationships. An understanding of these genetic/metabolic relationships provides new directions and opportunities for development of regimens for the prevention and treatment of prostate cancer. Important insight into the genetic/metabolic requirements of the prostate malignant process is now evolving. Most importantly at this time, an appreciation and recognition of the genetic/metabolic significance and implications in the development of prostate malignancy is imperative; and much needed research in this area is essential. Hopefully, this review will help to achieve these goals.

Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans https://www.ncbi.nlm.nih.gov/pubmed/28152549

Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

Zinc, aging, and immunosenescence: an overview https://www.ncbi.nlm.nih.gov/pubmed/25661703

Zinc plays an essential role in many biochemical pathways and participates in several cell functions, including the immune response. This review describes the role of zinc in human health, aging, and immunosenescence. Zinc deficiency is frequent in the elderly and leads to changes similar to those that occur in oxidative inflammatory aging (oxi-inflamm-aging) and immunosenescence. The possible benefits of zinc supplementation to enhance immune function are discussed.

Zinc homeostasis and immunosenescence https://www.ncbi.nlm.nih.gov/pubmed/25022332

For more than 50 years, zinc is known to be an essential trace element, having a regulatory role in the immune system. Deficiency in zinc thus compromises proper immune function, like it is observed in the elderly population. Here mild zinc deficiency is a common condition, documented by a decline of serum or plasma zinc levels with age. This leads to a dysregulation mainly in the adaptive immunity that can result in an increased production of pro-inflammatory cytokines, known as a status called inflamm-aging. T cell activation as well as polarization of T helper (Th) cells into their different subpopulations (Th1, Th2, Th17, regulatory T cells (Treg)) is highly influenced by zinc homeostasis. In the elderly a shift of the Th cell balance towards Th2 response is observed, a non-specific pre-activation of T cells is displayed, as well as a decreased response to vaccination is seen. Moreover, an impaired function of innate immune cells indicate a predominance of zinc deficiency in the elderly that may contribute to immunosenescence. This review summarizes current findings about zinc deficiency and supplementation in elderly individuals.

Zinc(II) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line. https://www.ncbi.nlm.nih.gov/pubmed/20524045?dopt=Abstract

Treatment of MCF-7 cells with tamoxifen induced vacuole formation and cell death. Levels of the autophagy marker, microtubule-associated protein light chain 3 (LC3)-II also increased, and GFP-LC3 accumulated in and around vacuoles in MCF-7 cells exposed to tamoxifen, indicating that autophagy is involved in tamoxifen-induced changes. Live-cell confocal microscopy with FluoZin-3 staining and transmission electron microscopy with autometallographic staining revealed that labile zinc(II) ion (Zn(2+)) accumulated in most acidic LC3(+) autophagic vacuoles (AVs). Chelation of Zn(2+) with N,N,N’,N’-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) blocked the increase in phospho-Erk and LC3-II levels, and attenuated AV formation and cell death. Conversely, the addition of ZnCl(2) markedly potentiated tamoxifen-induced extracellular signal-regulated kinase (Erk) activation, autophagy and cell death, indicating that Zn(2+) has an important role in these events. Tamoxifen-induced death was accompanied by increased oxidative stress and lysosomal membrane permeabilization (LMP) represented as release of lysosomal cathepsins into cytosol. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) blunted the increase in Zn(2+) levels and reduced LC3-II conversion, cathepsin D release and cell death induced by tamoxifen. And cathepsin inhibitors attenuated cell death, indicating that LMP contributes to tamoxifen-induced cell death. Moreover, TPEN blocked tamoxifen-induced cathepsin D release and increase in oxidative stress. The present results indicate that Zn(2+) contributes to tamoxifen-induced autophagic cell death via increase in oxidative stress and induction of LMP.

Ionophores as cancer chemotherapeutic agents https://patents.google.com/patent/US20060040980A1

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?page_id=1794

Related Articles


85 thoughts on “Unlocking Zinc’s Potential to Fight Cancer

  1. another great article D, thanks for your effort. wouldn’t you still chelate Copper instead of supplementing with zinc? is it safe to do them both simultaneously?

    1. Thanks Pouya and nice to hear from you! Actually Disulfiram has an action on Copper as well in a similar way as on Zinc. There is an entire science on that too and I would like to address the subject asap since it is very interesting. One way would be to chelate Copper and we discussed that in the context of TM. The other approach is to get it inside the cell with Disulfiram so that we reach high intra cellular levels. There is more to say here but I will better address the subject in another post. Answering your seccond question, I do not see a reason why it would not be safe to use Disulfiram (or other Zinc ionophore) + Zn and TM at the same time.

        1. Why do you think Pouya that there is a risk of Copper deficiency when combining with TM with Disulfiram and Zn? It is true that you may end up with a lower blood levels of Cu vs TM alone as Disulfiram will push part of it inside the cells.

          1. I guess because I was under this impression that supplementing with Zn reduces Cu serum levels and visa versa so adding TM would further potentiate the approach.

      1. Have you had a chance to look further into DFF and copper? I’m pretty sure not all types of cancer cells accumulate zinc at levels higher than normal cells. I am pretty sure breast cancer cells do, melanoma perhaps too, but from what I read, most cancer cells do not. (But I’ve read many times that cancer cells have generally a higher need for and concentration of copper than normal ones. There was a study a year ago in Stanford where they used copper isoform as a PET scan tracer in breast cancer, and it showed the tiniest mets, reportedly.) Since the increased (vs normal cells) demand for the metal that DSF binds to is what gets DSF into cancer cells, copper may be more effective for some or many cancers. But copper supplementation terrifies me. But so would iron, and that works with artemisinin. Also, do we really want DSF to chelate our zinc supply, given that a higher zinc:copper ratio seems favorable but is difficult to achieve? It would be interesting to know if DSF has a preference for chelating one metal over another. I keep meaning, then forgetting to, write to some study investigators for insights. The way I’m interpreting the research so far, it would be best to use whichever of those two metals your cancer cells are hoarding at higher levels than normal cells. If, say, your cancer cells use only about as much zinc as your healthy cells, the DSF would be dispersed throughout your body rather than preferentially be attracted by and thereby attack your cancer cells. I could be wrong, of course; I’m not a scientist. Would love to get educated input!!! I mean, sure, I get that DSF is a zinc ionophore, and that that’s a way of getting more zinc (and reach toxic levels) into cancer cells that otherwise wouldn’t accumulate it, but how would that not also affect healthy cells, if those cancer cells wouldn’t have a higher demand for zinc to start with?
        Here’s a paper that suggests that disulfiram has an affinity for copper over zinc, and forms a more stable complex with copper than with any other metal. Therefore, while it is terrifying to supplement copper when one has cancer, it looks copper may be the preferable metal to use with DSF, especially if one’s cancer accumulates copper. (I’m trying to find out if mine does.) I still don’t understand why the protocols in the trials call for taking copper in the evening, DSF in the morning, since one wants a complex to form. It that to prime the cancer cells with copper, or to get copper into the circulation first? I believe DSF gets cleaved into its active metabolites in the acidity of the stomach, then forms the complex in the blood. Would that explain the timing of dosing? Anyway, below the paper. It’s not in cancer but tuberculosis. I’m posting it in an effort to elucidate how DSF interacts with metals, while trying to decide whether to use it or not, and while supplementing with which metal. I am starting to think that zinc supplementation would still be safe and maybe even a good idea while on DSF and copper. (I’m deducing this from the paper, perhaps incorrectly.)I would love your opinion. Thanks!

  2. Very interesting article! I’m very much into copper chelation and would might believe that this effect of zinc (that it binds and excretes copper) is the most important anti-cancer effect of zinc? Also something very important is going on when it comes to the importance of zinc/copper ratio when it comes to development and progression in cancer disease. One of the reasons that I believe that copper is the key player here, is because of this study: https://dailyreckoning.com/the-link-between-copper-and-cancer/ where 75 stage 3&4 TNBC/tripple neg. breast cancer women were started with the copper chelator TM (Tetrathiomolybdate) – as you also mentioned in comment above – after 5 years 63 of these women were CANCERFREE! With TM as single drug treatment. I have not seen results like this ever in conventional or alternative treatment. And this with literally no sideeffects. I’m a doctor myself and our research has shown that it does not work anti-angiogenic and reduces progenitor cells from bonemarrow, but it also inhibits EGFR and important pathways like LOX and Src, that most solid cancers use to progress and metastasize. I’m having really high expectations for this drug and am using it against lungcancer myself. I believe it could be a complete gamechanger! Will be happy to share notes if you’re interested.

    1. Hi Anne Sofie,

      I very much agree: cooper chelation s a very relevant approach. I actually do not understand why it is not used more and why people are not triggered by its potential. I did wrote sometime ago a post on TM https://www.cancertreatmentsresearch.com/tetrathiomolybdate-tm/ and there was also a very relevant comment by one of the visitors who saw his girlfriend cured of ovarian cancer while using TM https://www.cancertreatmentsresearch.com/read-this-comment/ (I now realize I should change the title of this last link into something more representative). Thank you very much for the link you shared above. I did not know about that small study having such great results! These are the kind of results that should make it around the world. I am sorry to hear about the challenges you are facing and very much hope and expect (based on all the evidence) that you will see great results with TM. It will be my pleasure and that of the readers to see updates from you regarding the use of TM, and also on anything else that you may find relevant. Your experience as a doctor is also very much appreciated here.

      Kind regards,
      Daniel

    2. Hello Anne Sofie.
      We would like to use TM for my dad who has metastatic stomach cancer and whose condition has greatly deteriorated in recent weeks. We live in France, in the Paris region. I know that the use of TM requires regular blood sampling and a dose adjustment, and I would like to ask you if you can direct us to someone who can help us for these two steps, so we can try to help dad without much risk.
      Thank you very much.

  3. Dear Daniel, friends.
    I hope this gets to be read because i believe it to be a little more important as a comment than others i’ve made in the past.
    I feel, just feel…. that “the key” in fighting cancer is an analogue to the Trojan Horse Computer Virus, it may be what we are looking for.

    This article here, reminded me about the Gallium one.

    Many thanks,
    Alex

    1. hey Alex,

      It might be a good idea. Cancer can grow and spread especially because immune cells dont recognise them as such. Similarly, I hope humanity finds a weapon that is mistreated by cancer as a “cancer friendly” tool. To be honest, i dont anything about Gallium but 3-bp is resonating with the idea.

  4. Thank you very much Daniel , impressive article

    Its always helpful for me and sure for a lot of peoples who are reading here

    we appreciate the hard time you are giving us writing life saving information for the sake of humanity and people who are suffering around the world

    personally I’m sorry because I’m still that kind of a person who are taking much more than giving help , i wish to be helpful and not just utilizing and applying these treatments in real life , I’m doing my best to be helpful one day soon

    speaking about utilization , when i completed reading this article , i thought i could start it immediately as its available and cheap

    but i remembered the 3-BP article , Disulfiram may antagonize the effect of 3-BP , so it looks like I’m going to put this strategy on hold as long as I’m still giving 3-BP to my mother , but it will be next

    Thank you always my friend

    1. Thank you, Jandro. Yes, we discussed in various places the drugs targeting mito, including Doxycicline. I intend to write at some point a post on this subject as well. My wife and I did found Doxy very helpful as we used it from time to time, but as an antibiotic it has its drawbacks.

  5. I forgot, regarding to previus mesage, clioquinol block dna synthesis in fungi and protozoal, chloroquine growth in malaria and amebiasis. I find very interesting similarities between infections and cancer. Zinc is a cofactor for enzimes reactions, but i dont know exactly why helps. Maybe disbalance of growing.. who knows.

  6. Hi everyone.

    I didnt know if write in this post or other, i was reading about disulfiram and took me to inhibition of Aldh, a marker of csc, but unluckly not all types:
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423215/
    Here highlight citral as best inhibitor of aldh1a3, an oil from the peel of lemon. Has someone listen anything about citral? For eating? Where to get?
    Daniel, a lot is writen about Aldh, detoxificant enzimes that for sure is a key to unlock cure!

    1. Hi Jandro,

      Thanks for pointing this one out. Citral seems to be accessible online as a supplement. For example http://www.supervits.com/vitapurity-citral-100-caps-p5223.aspx (although is possible that this company was shut down recently based on an FDA warning I have seen)
      I will also dive deeper into ALDH
      Interesting point is that their result are suggesting only the nano particle encapsulated version of Citral works, due to the more effective tumor reach.

      1. Zinc has antibacterial activity and somehow day by day is apearing that is not just one crazy cell that doesnt stop to replicate, is that with the help of some bacteries;

        https://www.ncbi.nlm.nih.gov/m/pubmed/28753429/?i=16&from=colorectal%20cancer&sort=%5Brelevance%5D
        This one is strictly anaerobic, thats probably the link with therapies that suport O3 (ozone).
        This make me think that one isolated culture of cell could not be enought, cos cancer use the bacteries to go on growing, and that bacteries are not in the dish of the laboratory.

  7. These last days i always somehow reminded myself of copper, zinc, my small childhood experiments with these metals, with acids, vegetables, electronics, primitive batteries.
    Something i found here that may be of interest https://www.mayoclinic.org/diseases-conditions/wilsons-disease/diagnosis-treatment/drc-20353256
    The drugs are used to treat Wilson’s disease
    I found it fascinating that these two metals would matter so much and iron… there’s something electric going on in there for sure.
    To top it off there’s sodium written all over it. Idk, most likely i’m just throwing words without even understanding anything.
    Best of luck,
    Alex

  8. Hi Daniel, Jcancom, Marcos, Johan, Ovidiu, and all other amazing people on this site,

    I would like your thoughts on clioquinol as a zinc ionophor specifically for prostate cancer, versus Disulfiram and Chloroquine. My husband has been off of androgen deprivation (Lupron, zytiga) since May, 2018 with a PSA of 300mg/day).

    With gratitude,
    Shanti

  9. Hi All-

    I would like your thoughts on clioquinol as a zinc ionophor specifically for prostate cancer, versus Disulfiram and Chloroquine. My husband has been off of androgen deprivation (Lupron, zytiga) since May, 2018 with a PSA of smaller than 0.006, however, his last reading was 0.028, still very low but enough to let us know that the cancer is active. We are putting together a strategy as we would like to keep him off ADT and the earlier we are aggressive, we believe we will have a better outcome. The manipulation of zinc seems especially relevant to prostate cancer (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474672/).

    I came across these three articles, which build on each other, on clioquinol and zinc as a prostate cancer treatment approach:

    Evidence that Human Prostate Cancer is a ZIP1-Deficient Malignancy that could be Effectively Treated with a Zinc Ionophore (Clioquinol) Approach (2015)
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531383/

    Zinc Ionophore (Clioquinol) Inhibition of Human ZIP1-Deficient Prostate Tumor Growth in the Mouse Ectopic Xenograft Model: A Zinc Approach for the Efficacious Treatment of Prostate Cancer (2016)
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751054/

    A Proposed Efficacious Treatment with Clioquinol (Zinc Ionophore) and Cabergoline (Prolactin Dopamine Agonist) for the Treatment of Terminal Androgen-independent Prostate Cancer. Why and How? (2019)
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392423/

    In the first two papers, the authors establish that clioquinol is effective at increasing zinc levels in prostate cancer cells and that mice given intraperitoneal (IP) 30mg clioquinol/kg every other day for 5 weeks had “suppressed tumor growth by ~85%; and similarly decreased the weight of the tumors by ~78%.”

    The third paper proposes a treatment in humans using 3% clioquinol /1% hydrocortisone cream and cabergoline (to suppress prolactin, the assumption is made that individuals trying this protocol would be castrate resistant and on androgen deprivation).

    We are concerned about side effects with Disulfiram, Chloroquine has the added benefit of autophagy inhibition…. Perhaps chloroquine could be combined with clioquinol?

    Do you think clioquinol 3% cream would yield a therapeutic dose of clioquinol? The human equivalent dose (HED) of clioquinol for a 77kg human (my husband) for the mouse studies in the papers above would = 89mg clioquinol/ day (or 178/every other day day). In the third paper the authors suggest a “3% clioquinol cream could be initially applied to ~2 inch area of skin, perhaps once a day. If no adverse side effects become apparent, the treatment might be increased.”

    I was surprised the authors suggested that 3% clioquinol cream would be effective as it doesn’t seem approximate the HED unless the ‘best case’ of 40% absorption is achieved (Transdermal absorption may be between 2-40%) and about 7.5g of cream are applied daily. https://pubchem.ncbi.nlm.nih.gov/compound/Clioquinol#section=Absorption-Distribution-and-Excretion.

    Perhaps my questions don’t have answers at this time, but if anyone has any insights/thoughts on clioquinol vs disulfiram vs chloroquine for zinc ionophor purposes, the efficacy of a 3% clioquinol cream, or combining clioquinol with chloroquine, I would love to hear them.

    Note: Oral clioquinol has limited availability because it was withdrawn from the market in several countries due to toxicity concerns (myelo-optic neuropathy), but at doses much, much higher than the HED of 89mg/day (https://www.ncbi.nlm.nih.gov/pubmed/18812216/ seems toxicity concerns start at higher than 300mg/day).

    With gratitude,
    Shanti

    1. Shanti, I am glad that you have discovered this line of research as the metabolic aberrations in prostate cancer cells appear to be of central importance. Yet, I am sorry that you have not been more aware of this potential treatment path before. On a forum such as this, gems are often missed due to the sheer scale of the cancer research that we try and cover. It is unfortunate that we have not been able to communicate such research more effectively to those on forum.

      Researchers have been studying this idea for decades and decades, they continue to report largely the same results and no one seems to pay attention to them. It must be extraordinarily frustrating, prostate cancer is the leading cancer killer in non-smoking men.

      It is surprising how effective metabolic approaches can be (in vitro and in vivo) in prostate cancer.
      https://www.ncbi.nlm.nih.gov/pubmed/30928407
      Due to the metabolic changes, prostate cancer cells appear to be quite vulnerable to 3-BP.
      This might not be immediately apparent on a PSA test, though as the article notes, the metastatic potential was greatly reduced in the study.

      I am also excited about the potential for acetate scans in prostate cancer. Acetate enters prostate cancer cells through MCT-1.
      As 3-BP also enters cancer cells through MCT-1, acetate scans could be used to find those prostate cancer patients who will respond to 3-BP treatment.
      https://www.ncbi.nlm.nih.gov/pubmed/27694168

      Vitamin D and testosterone in prostate cancer.
      https://www.ncbi.nlm.nih.gov/pubmed/30664926

      Here’s a patient report of untreatable androgen-independent prostate cancer that successfully used the 3% Clioquinol Cream plus 50mg zinc supplement/day and cabergoline treatment.
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6578577/

      Of course, with so much of the research that we follow, there are no clear unambiguous answers.
      There will likely never be phase 3 placebo controlled trials.
      However, metabolic research into prostate cancer is too compelling to ignore.

      1. Hi J,

        Thank you so much for replying to my long technical post, it means so much to me, and the links you posted are gems. My husband actually had an acetate scan just before starting androgen deprivation in May of 2017…….. and it showed lesions that were not picked up by bone scan and CT in the left lung, left sacrum and in the pelvic and abdominal lymph nodes….. I am so glad that you pointed out the increased potential of 3-BP with mets that show up on acetate scan!

        Also-thank you for the case study, I had not found that myself and it speaks exactly to what we are looking to do. I am not sure how useful the cabergoline will be in someone not on androgen deprivation or castrate resistant, so we will start off with the clioquinol and zinc and are also planning on adding Chloroquine as an additional zinc ionophor. We will keep cabergoline in the wings for potential use (but are open to other opinions).

        Hubbie’s vitamin D levels are in the 60s, he takes 6000IU /day.

        I will be posting later today or tomorrow our initial plan of attack for feedback from the forum, I’m now looking at fitting in 3bp. We just got my husbands latest PSA result, it is 0.053, up from 0.029 three weeks ago, we will be scheduling an axumin PET on Monday. Your post really lifted my spirits after seeing the increase in PSA this morning. The information and knowledge on this forum is amazing and cannot be found anywhere else on the web. We have been a bit complacent with 2 years now of PSA results less than 0.006, but the zinc approach and others discussed here have always been in the back of my mind. Thank you again for your help and your service to all of us here.

        Shanti

        _________________________________________________-
        Husband:
        62 yo male
        radical prostatectomy Feb 2017 with post-prostatectomy PSA of 5
        C11-Acetate scan showed mets to left lung, sacrum and abdominal lymph nodes
        zytiga + lupron + prednisone + xgeva May 2017-May 2018 with PSA less than 0.006
        Discontinued zytiga and associated meds June 2018, PSA was less than 0.006 until June 2019 when it started to increase

        1. I am glad that you found my post helpful. A team effort does extend out the range of possible treatments that we can be made aware of.

          “Thirteen of 22 patients (59%) with serum PSA 3 ng/mL had positive AC PET findings, whereas only 1 of 24 patients (4%) with serum PSA levels 3 ng/mL had positive findings.” (see Figure 4)
          https://www.ncbi.nlm.nih.gov/pubmed/12679398

          Your husband’s 5 PSA at time of AC PET suggests that he was in the boundary zone where the scan could report positive or negative. The current PSA below 1 from the article’s results suggests that he would now have a negative AC PET.
          Would have to consider though the exact progression status of the patients from the article. Possibly after a first round of successful treatment MCT-1 levels remain elevated even at low PSA levels.

          My hunch is that without enough prostate cancer present MCT-1 is not highly upregulated and so acetate (and by inference 3-BP) will not enter the cancer cells. The idea here is that in Figure 4 most of the men with negative AC PET scans had low PSA values. Most with high PSA values had positive AC PET scans. Since acetate uses MCT-1 as does 3-BP, it suggests to me that typical prostate cancer patients with high PSA levels should be responsive to 3-BP. This is especially true with PSA’s over 7.

          These patients might be an ideal treatment population for a 3-BP trial. One could first screen patients for entry by PSA and AC PET readouts, treat them with 3-BP and then repeat PSA and AC PET scan. This would be a powerful clinical approach as one could almost watch in real time as the cancer cells were destroyed.

          Yes, it was quite odd that we both searched for the same thing and found different results. The May 2019 article was as you noted extremely relevant. It might be helpful to keep in mind that cancer often is more “and” than “or”. Some cells probably are androgen-dependent; others androgen independent. While it might not greatly change PSA levels if a small colony of one of these were eliminated, it would help reduce the overall complexity and move you closer to a potential curative response. It is disappointing that clearer treatment instructions were not given. About all they said was apply 3% clioquinol cream. This is quite vague.

          “Those relationships are consistent with our understanding that the androgen-dependent cells and the androgen-independent cells are different populations of malignant cells.”

          {Wow, I thought my post had been gobbled by the software! D’s computer infrastructure typically saves posts in the cache so it can be recovered; on other forums posts are gobbled up and never seen again!}

          Best Wishes, Jcancom

          1. Hi Jcancom,

            I am not sure if the negative C11 acetate scans were due to the lower PSA individuals expressing less MCTs on their tumors, or simply that you need greater tumor volume to concentrate the radio active isotope to light up the scan. For example PSMA scans turn positive because you need enough tumor volume to concentrate the contrast enough to visualize.

            If I remember correctly, often times the outside of the tumor express the MCT because it has access to oxygen so that it can utilize the lactate in oxidative phosphorylation, the inside of the tumor can purely glycolytic since it has less oxygen access, and therefore expresses less MCT. From that stand-point, perhaps it is better to use 3bp before the tumors get too large…. Since his tumor expressed the MCTs before androgen deprivation, I would bet it still expresses MCTs. His scan really lit up with the C11 acetate, no ambiguity. Unfortunately, Dr. Almeida, who offered the scans in Phoenix, no longer offers them.

            From this paper: The Metabolic Phenotype of Prostate Cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474672/, “As noted above, later stage prostate cancer cells do begin utilizing aerobic glycolysis leading to an increased intracellular concentration of lactic acid. This build up of lactic acid is toxic so to compensate, cancer cells express monocarboxylate transporters (MCTs) to reduce intracellular lactate levels (Figure (Figure1).1). Prostate cancer cells have shown to be heterogenic in the level of MCT expression between patients. A more avidly MCT-producing phenotype has been correlated with a more aggressive cancer and worse prognosis (21). “

            Warmly,
            Shanti

            1. Thank you replying, Shanti.

              Yes, there is some confusion about the AC PET scans.
              Yet, it is tentatively impressive that they appeared to have had such a high yield of detection relative to FDG.

              “Imaging findings indicating a high probability of recurrent prostate cancer were identified in 14 patients (30%) by AC PET, versus only 4 patients (9%) by 18F-FDG PET. … ”

              Your point that we might be below the detection limit is well taken. Strangely the quote below appears to be saying what you suggested “… hence, AC PET will [find it?] (be) difficult [to identify cancer?] in patients with low serum PSA levels.”. It is only that they were missing a few words.

              “As shown in Figure 4, we found that AC PET findings were positive in 59% of patients with a serum PSA level > 3 ng/mL but in only 4% of patients with a serum PSA level ≤ 3 ng/mL. It is known that the serum PSA level correlates with tumor volume in prostate cancer; hence, AC PET will be difficult in patients with low serum PSA levels.

              I am also impressed that so many of the prostate cancer patients with PSA greater than 3 had positive AC PET. AC PET+ should mean MCT-1+. Thus, AC PET + should imply likely 3-BP responsive. This might be an easy tool for selecting patients for a 3-BP trial. It is especially encouraging that detection appears possible even at a level as low as PSA 3, though the article calls for further research to clarify this.

              “A limitation of this study is that the majority of lesions found by PET were not confirmed by objective reference standards. Thus, some of the additional yield of AC PET could represent false-positive findings. Further studies are needed to accurately determine lesion-by-lesion and patient-by-patient sensitivity. ”

              https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6578577/

              I had thought that one way to resolve the question of these possible false positives/negatives would be to dose with 3-BP between AC PET scans. One might guess that an AC PET scan that went from positive to negative after 3-BP treatment was truly positive, a positive that stayed positive actually a negative; a negative with decreased LDH readings etc. after 3-BP actually a positive, and a negative that actually stayed negative was truly a negative.

              That is interesting. Yes, there is a very large C11 AC PET study out of Phoenix. I think that they are working on certification for prostate cancer. I noted on the compass thread that prostate cancer patients with especially illuminated AC scans might consider a visit to Dayspring. Possibly the informed consent document should even make this connection clear to patients.

              The point that we have not made enough of on these forums is that MCT-1 expression is associated with more aggressive tumors. One really does not want 3-BP to be effective (because it indicates an aggressive tumor) , though if MCT-1 expression is present, 3-BP is one way to shut it down. The tumor then selectively becomes MCT-1 non-expressive which is a good thing (as you noted): tumor cells then become more restricted in their ability to excrete lactate (through MCT-1 at the very least).

              You also raise an important that I have intended to ask D about: Are not the hypoxic tumor cells near the tumor center much more vulnerable to 3-BP? At the necrotic hypoxic centre of the cancer, there is no choice but to be glycolytic. There is little if any oxygen! These are exactly the tumor cells that I should have highly expressed MCT-1. They need to export large amount of lactate, likely through MCT-1, because OXPHOS is shut off (without oxygen it would be impossible). My reading of D’s past statements seemed to suggest that he saw 3-BP effectiveness more on the “rim” or oxygen side of the tumor.

              Best Wishes, Jcancom

            2. Hi J,

              Unfortunately, the imaging center in phoenix is no longer conducting clinical trials. Dr. Almeda, who managed center and trial has closed it down and gone into private practice. He must have run thousands of scans there, including ours. I had the feeling based on my last conversation with him, that the superior results of PSMA scan in several trials may have caused him to change course. The only place I could find that offers it in clinical trial context is here: https://clinicaltrials.gov/ct2/show/NCT02715583?term=prostate+cancer&recrs=ab&cond=acetate+PET&cntry=US&rank=1.

              Prostate cancer tends not to be glycolytic until later stages (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474672/), so I think the MCT1 expression and acetate uptake reflects the cancers acetate appetite to use it in de novo lipid synthesis rather than glycolytic status http://jnm.snmjournals.org/content/57/Supplement_3/30S.full. Nonetheless, it does indicate MCT1 expression and, therefore, a door for 3bp. Prostate cancer does seem to be sensitive to 3BP, will prostate cancer that express MCT1 without being highly glycolytic still be as responsive to 3bp?

              Regarding the cells on the outside of the tumor being more sensitive to 3BP, I can’t find D’s post right now, but that is right, the cells on the outside of the tumor would have highly expressed MCT1 to import the lactate they had previously exported through *MCT4*, the access to oxygen would allow them to use the lactate in oxphos. Even though the inside of the tumor is likely even more glycolytic and the expression of MCT4 would be high, MCT1 may not be so high because the cells can’t oxidize the lactate due to lack of access to oxygen, therefore, they are not as sensitive to 3BP.

              Warmly,
              Shanti

          2. Hi Jcancom,
            Thank you for pointing out that some of the cancer cells may be androgen-independent and these could be influenced by the cabergoline. In the paper I found the proposed dose was 3% over a two inch area, once a day with potential to increase, still rather vague. On the Health Unlocked forum, a poster stated they had been prescribed a 4% clioquinol cream, applied twice daily, by Dr. George Yu along with cabrgoline: https://yufoundation.org/about-us. He reported very good results, but he was also doing other therapies, so wasn’t sure what to attribute it to: https://healthunlocked.com/advanced-prostate-cancer/posts/140021711/has-anybody-been-prescribed-clioquinol.
            Warmly,
            Shanti

    1. Hi Shanti,

      I found the issue. There is a bug in Word Press so that if you add the sign “<" in a comment and ">” at the end, WordPress will cut everything else between “<" and ">” as it will think that is a command.
      After removing “<" and ">” in your comment, the comment looks as intended.

      Kind regards,
      Daniel

  10. I remember reading those papers and thinking it would be a good idea to use clioquinol cream recatally as when we perform a digital rectal exam, along with zinc orally. I don’t know if it would harm the rectal mucosa though, but it’d be worth trying

  11. Hi Yudaitheska,
    Of course, good thinking for a way to get increased absorption. Unfortunately, I have only been able to get my hands on clioquinol 3% with Betamethasone .1% and I am hesitant to use Betamethasone down yonder long term. At some point, we may try to get a clioquinol compounded cream, at which point we’ll consider that application.
    Best,
    Shanti

  12. Do you think hydroxychloroquine is also a zinc ionophore (as alternative to chloroquine , less side effects)?
    Using it as part of McLelland protocol.

    1. Good question Myriam. While I expect Hydroxychloroquine will be an ionophor as well due to chem structure similar to that of Chloroquine, I would need to study more this point to be 100% that is the case. I did a quick search in literature but there is nothing that comes up fast to answer the question. Please remind me again in a few weeks and I will try to go deeper in this subject.

  13. Article below on metal content analysis of chondrosarcoma tumor samples shows multiple discrepancies from normal bone.

    “The Silver, Cobalt, Chromium, Iron, Mercury, Rubidium, Antimony, Selenium, and Zinc Contents in Human Bone affected by chondrosarcoma”
    https://openaccesspub.org/JHOR/article/190

    Could targeting multiple metal content discrepancies give better results?

    1. This is indeed a relevant area related to some weak points of cancer. Interfering with ion dynamic and/or using supplements/drugs to interact with the metals accumulated in cancer cells (as artemisinin or vitamin C is doing) and generate ROS are relevant ways. This also offer the opportunity for effectiveness of electro-magnetic fields based treatments.

      Kind regards,
      Daniel

      1. Hi Daniel

        yes , i’ve read artemisia related article.
        I was asking whether co-administration of iron and zinc/copper related therapies can be done at same time?
        shooting from 2 sides should leave less space for cancer to escape.

        Best Regards

        1. Hi Asafsh,

          Yes, I realise you know about Arte. 🙂
          I just wanted to make the point that we have multiple tools to do what you propose, by addressing at least two related mechanisms: ion dynamics and ROS generation. Otherwise, shooting from 2 sides makes sense to me too.

          Kind regards,
          Daniel

          1. Hi Daniel

            Thank you for clarification.
            Not sure whether roles of copper and iron are completely understood today.
            https://www.sciencedirect.com/science/article/pii/S0167488916300167

            and seems iron and copper quite connected to each other
            https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460475/
            “Iron and copper have similar physiochemical properties; thus, physiologically relevant interactions seem likely. Indeed, points of intersection between these two essential trace minerals have been recognized for many decades, but mechanistic details have been lacking. Investigations in recent years have revealed that copper may positively influence iron homeostasis, and also that iron may antagonize copper metabolism.”
            clinical trial for copper only deficiency using TM resulted in only 31% SD at most for around 34 weeks.

            curious whether by modulating iron and copper level at same time it will be possible to weaken tumor cells enough to be killed by third low harm therapy.

            Best Regards

  14. Hi Daniel,

    I’m about 3 years out from my cancer diagnosis/treatment. I’ve been very strict with my diet for most of the 3 years(mostly vegan with wild salmon) and intermittent fasting. I’ve started feeling a tingling/tickling feeling in the spot where my tumor was (if I eat something on the sweeter side/or carbs) and am concerned that the cells are awakening. I’m hoping you can help me narrow down some places to start on my plan to prevent that/shut it down.

    It was breast cancer ER+ PR- HER 2 -. Stage 1. First they said grade 2, then upgraded it to 3. Clear nodes. It’s my understanding from the doctors that the fact that the tumor was PR- makes it more aggressive. It seemed to grow after the biopsy and get more aggressive after the biopsy.

    Did lumpectomy, biopsy site cleaning and seed trail cleaning and very wide margins. No radiation (left side) or chemo.

    I did not have a lot of other information about the tumor, so I requested the supplemental individual gene scores used to calculate the recurrence score that Genomic Health provided – OncotypeDX Breast Recurrance Score report. They give the gene name and then the single gene score. I looked them up in an attempt to see which ones were worrisome. I’ve included it in case that it would help.

    Bc12 11.2
    SCUBE2 7.4
    GRB7 7.3
    GSTM1 8.9
    CD68 9.6
    BAG1 8.9
    Cathespsin L2 4.9
    Stromelysin 3 12.2
    Survivin 6.6
    Ki-67 7.2
    STK15 6.1
    Cyclin B1 5.3
    MYBL2 5.9
    Beta-actin 14.6
    GAPDH 11.0
    RPLPO 11.8
    GUS 5.0
    TFRC 7.6

    Been treating myself for parasites with Fenbendazole 10 mg/kg/day (in 2 divided doses) 14 days. Then a one day break, then Ivermectin 12 mg, 2 x day, for 3 days. One day break, then back on the Fenben. Once a week I take Pyrantel Pamote in divided doses for one day.

    So far so good. Seem to be moving them out (they are/were in the liver and bile ducts (pancreas?) as well as the veins in my back. I have Praziquantel and will use that with the Ivermectin next after this protocol. Doing coffee enemas during break days as well a garlic enema. It helps to get the toxins out. I was very heavily infected (vegan diet?)

    This is what I’m currently taking. If you see anything that I shouldn’t be taking or that should be adjusted or added to, I’d greatly appreciate it. I’m very concerned about the cancer recurring/spreading and want to address it head on.

    Multi vitamin w/o iron or copper
    Vitamin D3 5,000 – 10,000 per day (adjust seasonally I live in the North) Just ordered one that is 5,000 IU and includes 50 mg K2 (M7 from fermented chickpeas)
    Berberine – 500 mg Berberine Aristate root extract 3x day with meals – 10-14 days on, then a break for 7- 14 days.

    Milk Thistle Extract – 300 mg Daily at bed time
    Dandelion Root 100 mg daily – it’s in the milk thistle capsule
    Artichoke Leaf – 50 mg daily – also in the milk thistle capsule

    Magnesium Glycinate 400 mg daily at dinner
    Zinc Piconilate 50 mg

    My copper zinc levels are out of whack. Cannot tell if it’s the parasites or the cancer. Been heavily supplementing zinc to correct the balance and despite that, my zinc went down.

    My copper to zinc ratio is 1.75. My understanding is that .70 – 1.0 is a healthy ratio.

    I’ve read that coffee enemas can helps flush the extra copper out of the liver.

    I’ve read through articles on this site and understand that Aspirin is recommended sometimes as well as Cimetidine. I’ve also read (elsewhere) that Benedryl has anti cancer effects. I had highly elevated whole blood histamine 1939 nmol/L in May (and for the past 2 years). Have not checked it since doing the antiparasite protocol.

    Given that this cancer was/is ER+ & PR-, do you have any suggestions? I’m typically sensitive to medications/side effects, so I usually avoid them or start with a children’s dose or a small dose then work my way up. (except with parasite stuff, can’t go too low or they develop resistance).

    The tumor was close to the surface, so topical solutions would also be an option.

    Is vitamin C (corn free ascorbic acid) bad?
    Is coffee (decaf) really bad? It’s my treat in the morning.

    I’m a bit overwhelmed at the time (my sister just passed away from stage 4 lung cancer) and trying to figure out what is harmful and what will be beneficial and feeling a bit of a panic.

    Thank you so much. You have no idea how much it means to me to have someone I can ask that will give me a sincere, informed opinion. I’ve had terrible experiences with doctors with an agenda being less than truthful with me and using coercive control. Just makes me trust them even less and I feel very much alone in this fight.

    1. Dear Healing,

      Thank you for your question.

      I am extremely busy, and this is why I can only answer specific questions at this point. This is why I cannot give feedback on each of the points and questions above. But I can help with the following points:

      1. For any cancer patient I would consider going at least for a few months with high dose curcumin, i.e. 7 g .day or so
      2. Breast cancer patients would be could to use supplements containing Baicalein as well as the Boswellia Acid AKBA
      3. Cimetidine would be a drug that I would use to reduce the chance for mets, but having in mind the points made here https://www.cancertreatmentsresearch.com/tips-on-treatments-a-list-to-be-constantly-updated/
      4. Here is a lot of great info on Breast Cancer https://www.cancertreatmentsresearch.com/community/breast-cancer/
      5. I would contact Maria who is expert in coaching Breast Cancer patients https://www.healingnutritionofsonoma.com/

      I hope this helps.

      Kind regards,
      Daniel

      1. Dear Daniel,

        Thank you for your response. I understand that you’re busy and I appreciate your time and attention, so I’ll make it brief with specific questions.

        I have done lots of research and here’s my questions. If others have answers or Ideas, that would be great to.

        I discovered the fenben and Ivermectin paste I was taking had parabans in them and stimulated the cancer.

        I did more research on Cimetidine. I have low stomach acid (think that’s why the parasites had a field day) and it’s my understanding that there’s some concern that Cimetedine has some estrogenic properties.

        What dose is recommended to shut down a cancer for the following?:

        1. Baicalein
        2. Boswellia Acid AKBA
        3. Artemisian
        4. Berberine
        5. Meformin

        Any topical solutions for strongly ER+ breast cancer?

        Just started aspirin at night 81mg – I read doses of 75 -100 mg, and there’s a standard 81mg dose in the States.

        Doing this all natural.
        Thanks again!

        What dose of the following is generally recommended for the following:

        Bos

        1. Hi Bos,

          I agree with D’s recommendations. Optimal dosing for natural products in cancer treatment is not known but I think under-dosing is much more frequent than overdosing. Curcumin 7 grams a day is a good dose, less is probably not very effective. You might want to make a topical solution with curcumin. https://journals.sagepub.com/doi/full/10.1177/2211068216655524

          You might want to check https://synergiesforcancertreatments.blogspot.com/ for more information on dosing and coactive combinations.

          1. Hi Johan,

            It’s Healing – The Bos was a typing error – somehow my text got moved down while typing and couldn’t find it! Discovered it after I hit send. Oh well.

            Thanks for the information. The blog is helpful.

            I didn’t see a recipe for the topical solution in the article. It was likely in there, but it was pretty technical and over my head. I’m overwhelmed.

            I get the sense that this site is probably geared more to professionals or folks with way more experience than me. It’s challenging when facing cancer to get calm and do the research when your brain is in panic mode. I find it difficult to read through all the articles. Normally, that’s not a problem for me.

            I understand that optimal dosing is not known, but based on experience and feedback, I was hoping to get in the ballpark for the supplements I asked about.

          2. Hi @johan,

            What is your thoughts about taking a one big dosage of curcumin or would you split for example in two?

            I’m thinking to take about 9 grams, half mcs liposomal c3 and the other in regular c3 complex.

            Do you have the same idea when we thin in egcg too?

            Thank you

            Inaki

            1. Hi @johan,

              I´m trying to block glutaminosys as best is possible.

              I take lemon juice water with egcg, curcumin,honokiol, omega3 and Ursolic acid https://www.supersmart.com/es/tienda/deporte-actividad-fisica/ursolic-acid-complemento-0676

              I have two questions if it´s possible to know:

              -what dosage of ursolic acid is revelant for this purpose?
              -Can be improved the absortion of the ursolic taking something or it is fine with the lemon juice+ omega 3 fat.

              A big hug

            2. Hi Iñaki

              Regarding the UA dose: “UA and OA have been shown to inhibit the proliferation of non-small cell lung cancer A549 cells in a nude mouse model at low and high doses of 50 and 100 mg/kg bw, respectively. At 100 mg/kg bw, UA significantly inhibited the growth of the cells noted in tumor weight.” pubmed.ncbi.nlm.nih.gov/29264822

              Aprox 500mg UA for a 60KG person

              You´re taking curcumin so that helps with the UA, I think that´s fine, and take the curcumin with DHA, avoid Alpha-Linolenic Acid when you take curcumin.

              Saludos

  15. Hi Healing,

    Oral administration of skullcap polyphenols (200 mg per kg per day) to tumor-bearing mice displayed 50% reduction in tumor volume after 7 weeks of treatment https://pubmed.ncbi.nlm.nih.gov/17516867/

    So for a 60Kg human that would be approx 1000mg or 1 gram per day. Daniel will correct me if I am wrong.

    For Berberine a good dose seems to be 500 to 1500mg per day, in divided doses, and not every day of the week, ON-OFF 4-3 days.

    Curcumin 7 grams or more.

    Artemisinin, 500 – 1500mg per day, in divided doses. ON-OFF 5-2 days

    There are many ways you could try topical turmeric application, an easy way would be to make curcumin tea, let it cool, and mix with a little bit of glycerin.

    I would also look into Butyrate. The more I study cancer to more I notice the pivotal role it has in cancer occurrence and progression or regression. Health, or disease, does seem to start in the gut after all. Hippocrates said this over 2000 years ago and to me, it seems any cancer treatment should start there.

    1. Thanks, Johan.

      “Oral administration of skullcap polyphenols (200 mg per kg per day) to tumor-bearing mice displayed 50% reduction in tumor volume after 7 weeks of treatment https://pubmed.ncbi.nlm.nih.gov/17516867/

      So for a 60Kg human that would be approx 1000mg or 1 gram per day. Daniel will correct me if I am wrong.”

      Do you mean 20 mg per kg per day – based on your estimate of 1000 mg for a 60kg person?

      Curious on your take of not taking Berberine every day. Is there a benefit to not taking it every day? I currently take it in lieu of Metformin – and it also helps with parasites.

      I will try the tumeric tea idea topically.

      It’s my understanding that Frankincense & Myrrh essential oils are beneficial for cancer, so I’ve been applying them directly to the area and the surrounding area.

      1. Hi Healing,

        Based on that study in mice and converted for a human dose I got approx 1 gram (1000mg) for 60KG human, that would be 16,6mg/kg. Per day.

        About Berberine, depending on the dosage and especially if taken long term I think an ON-OFF schedule is a good idea. Berberine can cause gastrointestinal issues. Depends on well you tolerate it and how many other supplements you take.

        I’d continue the Frankincense, yes.

  16. My husband was diagnosed with prostate cancer a year ago; on ADT (Eligard) for 13 mo., had 8 weeks of Proton radiation that ended last June,
    started Zytiga in Sept.
    ALSO in Sept, he started taking Quercetin and Ionic Zinc
    Testosterone had been steadily going down since beginning of ADT, then PSA and T jumped in Nov. after starting 3 new things
    He stopped the Quercetin and T dropped and so did PSA
    then T started up again.
    I have now read Zinc can increase Testosterone
    YOUR opinion? I am thinking he needs to stop the zinc

  17. Wow, wasnt expecting to see negative results with Zinc on PSA. I have just purchased some zinc picolinate with a view to taking 50mg per day. All the research i have read to date is that zinc has a positive effect on PC tumours, in fact in nearly all cases, zinc is present in all healthy Prostate cells, whereas PC cells have a no zinc present, so surely that adds enough weight to say Zinc is beneficial.
    Im sure other regular PC posters on here, Shanti et al have seen positive bebefits by using zinc. Would be interested to see what others think.

    1. Purplegolfchic mentioned that testosterone went up, so that was probably the reason for the rise in PSA. My husband is currently taking a break from ADT/Zytiga, but when he is on them, his Testosterone is <5 (basically undetectable), taking zinc or quercetin does not change this. I do know some men have can have detectable testosterone on these meds and, although unusual, some even have a hard time keeping T below the target of <50. Zinc can inhibit the aromatase enzyme which converts Testosterone to Estrogen, theoretically increasing Testosterone, but in my husband's case, there was never any Testosterone around for the zinc to act on. As far as zinc being able to fight prostate cancer, we only saw a measurable impact when we added a zinc ionophore, in our case, clioquinol, along with the zinc.

        1. Hi Inabari,
          I am not sure if it is the best of the zinc ionophores, but we chose it because of the research that is specific to prostate cancer which you can read about starting at this post above:
          https://www.cancertreatmentsresearch.com/unlocking-zincs-potential-to-fight-cancer/#comment-8610

          Ideally, you use 3% cream 1G twice a day on thin areas of the skin. My husband could not tolerate that much and also can not tolerate continual dosing, so we use it intermittently as tolerated.
          Because we could also only find clioquinol cream mixed with betamethasone and I didn’t want to always be giving him the steroid, we did end up getting pure powdered clioquinol which I formulated with DMSO and water and that is what I use now transdermally to tolerance level.

          1. Hello Shanti! I hope things are going good with your husband. I remember you once said that your husband sometimes feels poorly when taking the high dose zinc w/topical clioquinol AND I was wondering if he Is taking copper supplementation since high dose zinc could impact copper levels…
            Un abrazo!

          2. Hello Shanti,
            I see you have a lot of knowledge and experience with treating PC.
            I’m intrested in your recipe for clioquinol topical mixture with DMSO. Would you be so kind to share how to make and use it? How much of zinc did your husband take when on clioquinol?
            I was looking for the original cream but I cannot obtain it in EU and the pure clioquinol would be better to use.
            Thank you in advance!

    1. Hi, the product you refer to already has zinc (in the form of zinc acetate) with a Proprietary Zinc Complex including zinc ionophores.

      You can take magnesium alongside zinc, that’s fine.

Leave a Reply