Prostate cancer - Discussion Board

Therapeutic interference of SREBP-mediated lipid metabolism by E-Xanthohumol attenuates prostate cancer progression

johan — Sun, 30 Aug 2026 16:36:25 +0000

Jonathan Viehoever, Naveen Surya Velmani, Vignesh Basavaraj, Lahiru Gamage, Kai-Cheng Chan, Praveenkumar Basavaraj, Wen-Chin Huang,
Therapeutic interference of SREBP-mediated lipid metabolism by E-Xanthohumol attenuates prostate cancer progression.
https://doi.org/10.1016/j.bcp.2026.117859.

This preclinical study tested whether combining two plant-derived compounds—xanthohumol (from hops) and ursolic acid (found in foods such as apples, cranberries, and thyme)—could slow prostate-cancer development more effectively than either compound alone.

Researchers conducted experiments in six human and mouse prostate-cancer cell lines and in two mouse models:

- Mice implanted with HMVP2 prostate tumors.
- HiMyc mice genetically predisposed to develop prostate cancer.

The animals received standard food or food containing xanthohumol, ursolic acid, or both. Each compound constituted 0.2% of the supplemented diets. Synergy was assessed using the Bliss independence model.

The combination reduced cancer-cell survival and colony formation more strongly than either compound alone across all six tested cell lines. It also altered proteins governing cancer growth and cell-cycle progression: phosphorylated STAT3, cyclin D1, c-MYC, Cdc6, and phosphorylated Rb decreased, while the cell-cycle inhibitor p21 increased.

In the implanted-tumor model, the combined diet produced significantly smaller tumors than the control or either single-compound diet. The effect met the researchers’ criterion for synergy from day 21 onward. Tumors also showed:

- Reduced polyamine synthesis and lower levels of metabolites involved in that pathway.
- Changes consistent with suppression of epithelial-to-mesenchymal transition, a process associated with cancer invasion.
- Increased E-cadherin and decreased Twist1.

In HiMyc mice, the combination reduced progression from precancerous lesions to adenocarcinoma. This appeared to involve endoplasmic-reticulum stress, activation of the unfolded-protein response, and apoptosis. Neither compound alone produced comparable protection at the doses tested.
Body weight and food intake were not adversely affected, suggesting the mice tolerated the diets well.

The results support the biological plausibility of xanthohumol and ursolic acid acting together against prostate cancer through several mechanisms—disrupting growth signaling, slowing the cell cycle, changing tumor metabolism, suppressing invasive characteristics, and promoting cancer-cell death.

The limitation is that this was a laboratory and animal study, not a human clinical trial. Some experiments had small sample sizes—three replicates for several cell studies and approximately seven or eight mice per group in the implanted-tumor experiment—and some tissue analyses used pooled samples. The 0.2%-of-diet doses also cannot be translated directly into a safe or effective human supplement dose. Human absorption, metabolism, long-term safety, drug interactions, and clinical effectiveness remain unknown.

Drug Repurposing of Pantoprazole and Vitamin C Targeting Tumor Microenvironment Conditions Improves Anticancer Effect in Metastatic Castration-Resistant Prostate Cancer

johan — Mon, 16 Jan 2023 22:35:01 +0000

Abstract

"The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for Lu-177 or Ra-223 treatment. Drug repurposing as a cost-effective and time-saving alternative to traditional drug development has been increasingly discussed. Proton pump inhibitors (PPIs) such as pantroprazole, which are commonly used as antacids, have also been shown to be effective in cancer chemoprevention via induction of apoptosis in multiple cancer cell lines. Vitamin C is an essential micronutrient for human body, has been proposed as a potential anti-cancer agent. In this context, have we investigated the combination of vitamin C and pantoprazole for the management of metastatic castration-resistant prostate cancer (mCRPC). Six chosen human adenocarcinoma cell lines were used to investigate the influence of pantoprazole on the microenvironment of cancer cells (extracellular pH and production of exosomes). Tumor growth and tumor 18F-FDG uptake in PC3 xenografts were analyzed following varied treatment. Our in vitro Results have suggested that pantoprazole enhanced the cytotoxic activity of vitamin C by regulating pH values and production of exosomes in cancer cells. Moreover, the synergistic effect of pantoprazole and vitamin C was pH-dependent since pantoprazole was more effective at a slightly acidic pH. In vivo, the combined treatment using pantoprazole and vitamin C produced better therapeutic outcomes than treatment with vitamin C or pantoprazole alone, as demonstrated via tumor growth and uptake of 18F-FDG. Therefore, we suggest that pantoprazole combined with vitamin C could be as a possible strategy to manage mCRPC."

https://www.frontiersin.org/articles/10.3389/fonc.2021.660320/full

A systematic review and meta-analysis on overall survival, failure-free survival and safety outcomes in patients with metastatic hormone-sensitive prostate cancer treated with new anti-androgens

johan — Sat, 26 Nov 2022 14:44:40 +0000

https://journals.lww.com/anti-cancerdrugs/Abstract/9900/A_systematic_review_and_meta_analysis_on_overall.97.aspx

"The addition of either abiraterone, apalutamide, darolutamide or enzalutamide to ADT improves OS and failure-free survival in hormone-sensitive metastatic prostate cancer, albeit an increase in AEs."

Sodium Butyrate Induces Growth Inhibition and Apoptosis in Human Prostate Cancer DU145 Cells by Up-Regulation of the Expression of Annexin A1

johan — Sun, 25 Sep 2022 00:32:34 +0000

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074922

Conclusion
Our results support a significant correlation between NaB functions and ANXA1 expression in prostate cancer, and pave the way for further studying the molecular mechanism of NaB actions in cancers.

Synergistic effects of natural products in combination with anticancer agents in prostate cancer

johan — Wed, 21 Sep 2022 20:39:30 +0000

A recent review: https://www.frontiersin.org/articles/10.3389/fphar.2022.963317/full

Clioquinol Zinc Ionophore for Terminating Advanced “Decreased Zinc” Testosterone-Dependent Prostate Cancer: A Case Report

medline — Fri, 16 Sep 2022 12:59:21 +0000

ABSTRACT

In 2019, Costello et al. published the first successful treatment Case Report of a patient who presented with testosterone-dependent prostate cancer. That cancer is a “decreased-zinc” malignancy. The treatment was clioquinol zinc ionophore (3% Clioquinol Cream), which terminated the patient’s malignancy.

This second Case Report corroborates the 2019 Case report in employing clioquinol to terminate testosterone-dependent prostate cancer in patients. The two patient cases provide evidence that clioquinol will likely be effective for other patients. Now, oncologists and urologists have efficacious systemic chemotherapy for their testosterone-dependent prostate cancer patients. Then, for the first time, many or most of the 314,500 men in the U.S., and the 10 million men worldwide, who die of prostate cancer every year, can now be treated with clioquinol and cured of that cancer. We must make it happen.

Keywords: prostate cancer; testosterone cancer; prolactin cancer; treatment; clioquinol; cabergoline

INTRODUCTION

The Costello et al. 2019 case report , for the first time, identified a cure for a patient with testosterone-dependent prostate cancer; a “decreased zinc” malignancy. The treatment is clioquinol zinc ionophore; which binds zinc in the blood plasma and produces ZnClioquinol. The ZnClioquinol is transported to the testosterone-dependent malignant sites and releases its zinc into the malignant cells, which induces cytotoxicity that terminates the testosterone-dependent prostate cancer.

This second case report confirms the efficacy of clioquinol in another patient with testosterone-dependent prostate cancer. That corroboration is essential to employ clioquinol as the treatment for all or most patients with advanced testosterone-dependent prostate cancer.

PATIENT JG CASE REPORT

The following is the case report that I received from a patient in Sweden and was asked to review and provide an assessment. The case presents the chronology of events. Added are “italicized comments” of the Author. The intent of those comments is to provide relevant information for the benefit of the Reader. The patient is referred as “JG” to maintain anonymity.

March 27, 2019: F-PSMA/PET scan detected a localized malignancy at the periphery of the prostate gland. The scan was negative for lymph nodes or bone metastases.

F-PSMA/PET scan (Prostate-Specific Membrane Antigen) is specific and sensitive for the identification of prostate gland malignancy and for prostate metastatic sites.

October 9, 2020: PSA=2.71.

By itself, PSA=2.71 does not establish the presence or absence of prostate cancer in patients. The positive March 27, 2019 PSMA and the PSA=2.71 indicate the confined presence of the localized prostate malignancy.

December 8, 2020: PSA=2.23.

Several conditions are known to cause the expression of PSA (BPH; prostate inflammation; prostatitis; urinary infections). However, the PSA=2.71, PSA=2.23, and PSMA-positive scans, together are consistent with the identification of localized prostate gland malignancy. However, it is unusual for untreated localized cancer to persist for about 13 months.

December 8, 2020–January 7, 2021: Casodex (50 mg/day).

Casodex (bicalutamide) is an anti-androgen receptor agent that is employed for the treatment of testosterone-dependent prostate cancer. It suppresses the progression of the malignancy; however, it does not terminate the malignancy.

January 7, 2021: PSA=1.00; Prolactin=16.0. Cabergoline (0.25mg twice weekly) + Casodex

The PSA=1.0 indicates the success of the 30-day Casodex treatment in arresting prostate malignancy.

However, the implication of prolactin is perplexing. It raises the issue of the existence of prolactin-dependent prostate cancer. Unlike “decreased zinc” testosterone-dependent prostate cancer, prolactin-dependent prostate cancer does not exhibit any identifying biomarkers. Then why is the plasma prolactin concentration determined; which was in the normal range for men? Why was cabergoline the treatment for a patient with normocitricemia? It is the treatment for hyperprolactinemia patients with pituitary prolactinomas. Cabergoline inhibits the prolactin production and secretion of those adenomas. That results in hypoprolactinemia, which suppresses and ultimately terminates prolactin-dependent prostate cancer. In the absence of any evidence in the case report, the patient and/or his oncologist were knowledgeable of prolactin-dependent prostate cancer. It is likely that cabergoline was employed to protect against the development of prolactin-dependent prostate cancer in the patient. The cabergoline treatment achieves that prevention.

9th March 2021: PSA=0.68; Prolactin=3.0. Cabergoline + Casodex

Casodex is reducing the PSA-secreting testosterone-dependent malignancy and prevents the recurrence of testosterone-dependent prostate cancer. Prolactin=3.0 ng/ml demonstrates the Cabergoline inhibition of the pituitary production of prolactin.

June 2, 2021: PSA=0.73, Prolactin=2.3. Cabergoline + Casodex.

The successive PSA=1.00, PSA=0.68, and PSA=0.73 values indicate the Casodex arrest of the patient’s testosterone-dependent malignancy. However, another PSMA scan would be advisable to establish the absence of prostate malignancy. The Prolactin=2.3 ng/ml is the result of the cabergoline treatment.

July 3, 2021: Cabergoline; 3% Clioquinol Cream; Casodex.

3% Clioquinol Cream is the treatment for the “decreased zinc” testosterone-dependent prostate cancer. The Cream is applied to the skin and massaged into the dermis; the clioquinol enters the blood plasma to produce ZnClioquinol; which is circulated to malignant sites. The Zn is then transported into the malignant cells and induces its cytotoxic effects, which terminates testosterone-dependent prostate cancer.

August 2, 2021: PSA=0.62; Prolactin=1.1. Cabergoline; 3% Clioquinol Cream; Casodex; Vitex;

40 mg ZnPicolinate/day. Circulating Tumor Cell Count=0.

PSA=0.62 is indicative of clioquinol treatment efficacy in terminating “decreased zinc” testosterone-dependent prostate cancer. Prolactin=1.1 ug/ml is a 90% decrease due to cabergoline inhibition of the pituitary production of prolactin. That hypoprolactinemia prevents the development of prolactin-dependent prostate cancer.

ZnPicolinate is an over-the-counter zinc supplement to maintain sufficient plasma zinc for the formation of ZnClioquinol. Vitex is an over-the-counter agent that is employed to prevent prolactin production from agents such as estrogen, dopamine antagonists, serotonin, histamine, opioids, and other agents. That could result in the development of recurrent or new prolactin-dependent prostate cancer. The Vitex is taken daily to supplement the protective effect of cabergoline.

The Circulating Tumor Cell Count=0 reveals the absence of circulating metastatic cells. That demonstrates the efficacy of clioquinol and cabergoline treatment for the termination of advanced prostate cancer in patients. However, a CTCC count should be conducted prior to clioquinol treatment and 6 weeks following treatment. Then, the existence of metastases prior to treatment would result in a CTCC such as 5.4; which predicts impending patient death within 10-12 months. Then, the CTCC count=0 would confirm the efficacy of clioquinol treatment. That is the result for the patient in the 2019 case report.

September 17, 2021: PSA=0.60; Prolactin=0.9. Casodex; Cabergoline; Clioquinol

The low PSA and prolactin values show the continued absence of malignancies in the patient.

October 18, 2021: PSA=0.48; Prolactin=0.9. Casodex; Cabergoline; Clioquinol

Continued evidence of the efficacy of the chemotherapies.

March 9, 2022: Patient JG advises Dr. Costello that he has had no discomfort in his groin or any other symptoms of malignancy.

That is 5 months since August 2, 2021, CTCcount=0. The Patient’s statement of “no symptoms of malignancy” is an important indicator that he is cured of prostate cancer malignancy.

May 3, 2022: PSA=0.99; PRL=1.6 ng/ml; Casodex; Dostinex; Clioquinol; ZnPicolinate.

The low PSA and prolactin levels are continued evidence of the efficacy of clioquinol and prolactin; if it existed in the patient.

June 3, 2022: PSA=0.77; PRL=1.1 ng/ml; Casodex; Dostinex; Clioquinol; ZnPicolinate.

The values continue to exhibit the efficacies of the treatments. From September 17, 2021–June 3, 2022 (about 7 months), all indicators confirm that the patient is cured of testosterone-dependent prostate cancer.

July 5, 2022: Patient JG advises that he has no clinical symptoms in the groin or lower abdomen and that he feels well.

That is additional confirmation that the patient is cured.

DISCUSSION AND CONCLUSION

It is noteworthy that in 1999, 42 years ago , Liang et al. identified 2 types of prostate carcinoma cells: LNCaP cells and PC-3 cells. The LNCaP malignant cells developed as “decreased zinc” testosterone-dependent prostate cancer cells that are susceptible to cytotoxic effects of physiological zinc treatment. The PC-3 malignant cells developed as androgen-independent malignant cells (now recognized as prolactin-dependent prostate cancer cells) which are not “decreased zinc” cells. They are not susceptible to zinc-induced cytotoxicity.

Another important difference is the identification of testosterone-dependent prostate cancer via its secretion of PSA (Prostate-Specific Antigen) and via PSMA scan (Prostate-Specific Membrane Antigen). In contrast, prolactin-dependent prostate cancer does not exhibit any identifying biomarkers. The only procedure for its presence or absence is an MRI of PSA/PMSA-negative patients. An MRI detection of malignancy is indicative of prolactin-dependent prostate malignancy. That is confirmed by cabergoline treatment for 6 weeks, Then, another MRI should be negative. If the MRI is positive, the patient has another type of malignancy. This is a lengthy, costly, and necessary process to prevent patient deaths due to prolactin-dependent prostate cancer.

This case report corroborates the 2019 case report regarding the successful clioquinol treatment of patients with “decreased zinc” testosterone-dependent prostate cancer. Together, the reports corroborate the efficacy of clioquinol treatment for terminating that malignancy and curing patients of prostate cancer. However, an important difference is the issue of prolactin-dependent prostate cancer. The patient in the 2019 case, exhibited testosterone-dependent and prolactin-dependent cancer by the procedures described above. That case was the discovery of prolactin-dependent prostate cancer.

The conditions, in this case, did not establish the presence or absence of prolactin-dependent prostate cancer. The cabergoline treatment of the patient would terminate that malignancy if it were present. Otherwise, the patient unknowingly would have died of prolactin-dependent prostate cancer. That is the reason for my reference of prolactin-dependent prostate cancer as the “silent killer” that is responsible for most of the deaths due to prostate cancer.

The most important conclusion from these cases is that there are efficacious chemotherapies for both prostate cancers: clioquinol zinc ionophore for testosterone-dependent prostate cancer; cabergoline prolactin agonist for prolactin-dependent prostate cancer. Now, most of the 314,500 men in the U.S. and the 10 million men worldwide who are expected to die every year, for the first time, have efficacious chemotherapies to terminate their prostate cancer malignancies. It must be achieved!

https://mathewsopenaccess.com/full-text/clioquinol-zinc-ionophore-for-terminating-advanced-decreased-zinc-testosterone-dependent-prostate-cancer-a-case-report

Metabolomics-based phenotypic screens for evaluation of drug synergy via direct-infusion mass spectrometry

johan — Fri, 26 Aug 2022 20:25:10 +0000

Using a cancer drug library, we validated the drug screening, integrating isotope-enriched metabolomics data and computational data mining, on a panel of prostate cell lines and verified the synergy between CB-839 (Telaglenastat) and docetaxel both in vitro (three-dimensional model) and in vivo. The proposed unbiased metabolomics screening platform can be used to rapidly generate phenotype-informed datasets and quantify synergy for combinatorial drug discovery.

https://www.cell.com/iscience/pdf/S2589-0042(22)00491-6.pdf

Bromhexine, a mucolytic cough suppressant, may suppress prostate cancer metastasis

medline — Wed, 20 Jul 2022 15:26:54 +0000

TMPRSS2 is an androgen-regulated cell surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastasis. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-Met receptor tyrosine kinase signaling, and initiated a pro-invasive EMT phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment.

https://ncbi.nlm.nih.gov/pmc/articles/PMC4409786

Bromhexine is derived from the Adhatoda vasica plant and aids in the clearance of excess mucus, improving breathing and reducing cough. It was introduced into the market in 1963, and is widely available as an over-the-counter drug in many countries. Recently, bromhexine and its metabolite ambroxol have garnered interest for the potential prevention and treatment of COVID-19 due to their interactions with cell receptors in the lungs.

Inactivation of ATP citrate lyase by Cucurbitacin B: A bioactive compound from cucumber, inhibits prostate cancer growth

medline — Sat, 04 Jun 2022 14:29:37 +0000

Abstract

Prostate cancer, a leading cause of cancer-related deaths in males, is well recognized as having late disease on-set (mostly at age 60-70) and showing slow/latent disease development, and strategies to prevent cancer formation in late manhood may have significant health impacts. Cucurbitacin B (CuB) is a naturally occurring compound that is found abundantly in cucumbers and other vegetables, and it is known to exert anti-cancer activities (primarily via apoptosis-induction) in several human cancers. However, its chemopreventive potential for prostate cancer has not yet been investigated. Here, we reported that CuB significantly and specifically inhibited prostate cancer cell growth with low IC50 (~0.3 μM; PC-3 and LNCaP), accompanied by marked apoptosis (Caspase 3/7 activation, PARP cleavage, increase of Annexin V-Alexa Fluor 488 (Alexa488)+ cells and accumulation of Sub-G0/G1 population), whereas normal human prostate epithelial cells (PrEC) were CuB-insensitive. Using a chemopreventive model, pre-treatment of mice with CuB (2 weeks before PC-3 prostate cancer cell implantation) significantly reduced the rate of in vivo tumor-formation. A 79% reduction in tumor size (accompanied by marked in situ apoptosis) was observed in the CuB-treated group (with no noticeable toxicity) vs. controls at day 31. Strikingly, mechanistic investigations demonstrated that CuB drove dose-dependent inhibition of ATP citrate lyase phosphorylation (ACLY; an important enzyme for cancer metabolism) both in vitro and in the CuB-chemopreventive mouse model. Importantly, ACLY over-expression abrogated CuB's apoptotic effects in prostate cancer cells, confirming ACLY as a direct target of CuB. Thus, CuB harbors potent chemopreventive activity for prostate cancer, and we revealed a novel anti-tumor mechanism of CuB via inhibition of ACYL signaling in human cancer.

https://pubmed.ncbi.nlm.nih.gov/24690568

Cucurbitacin is a class of biochemical compounds that some plants – notably members of the pumpkin and gourd family, Cucurbitaceae – produce and which function as a defence against herbivores. Cucurbitacins are chemically classified as triterpenes, formally derived from cucurbitane, a triterpene hydrocarbon.

Cucurbitacins impart a bitter taste in plant foods such as cucumber, zucchini, melon and pumpkin.

https://en.wikipedia.org/wiki/Cucurbitacin

Triterpenes constitute a significant portion of the lipid substances of all plants; These compounds are precursors to steroids in both plants and animals.

https://en.wikipedia.org/wiki/Triterpene

White Button Mushroom --- Prostate Cancer

Kimster — Sun, 21 Mar 2021 12:03:56 +0000

Hi friends, just sharing the following here:

https://www.eurekalert.org/pub_releases/2021-03/tes-wbm031621.php

White button mushrooms could slow progression of prostate cancer

NEWS RELEASE: 20 MAR 2021

Mouse study suggests mushrooms may suppress androgen receptor activity

WASHINGTON--The chemicals present in white button mushrooms may slow the progression of prostate cancer, according to a mouse study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"Androgens, a type of male sex hormone, promote the growth of prostate cancer cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells," said lead researcher Xiaoqiang Wang, M.D., Ph.D., M.B. (A.S.C.P.), of the Beckman Research Institute of City of Hope, a comprehensive cancer center in Duarte, Calif.

"White button mushrooms appear to suppress the activity of the androgen receptor."

City of Hope's Shiuan Chen, Ph.D., the principal investigator of this project, previously conducted a phase one clinical trial of white button mushroom powder in patients with recurrent prostate cancer, which indicated that the mushrooms reduced levels of prostate-specific antigen (PSA) in the blood, with minimal side effects.

Heightened blood levels of PSA in men may indicate the existence of prostate tumors.

The new study aimed to understand the mechanism behind this finding.

The researchers studied the mushroom extract's effect on prostate cancer cells that were sensitive to androgen.

They also studied the extract's effect on mice implanted with human prostate tumors, which creates an animal model whose results would be more reliable as the research is translated to human clinical trials.

The researchers found that in prostate cancer cells, white button mushroom extract suppressed androgen receptor activity.

They also found that in mice treated with white button mushroom extract for six days, prostate tumor growth was significantly suppressed, and levels of PSA decreased.

"We found that white button mushrooms contain chemicals that can block the activity of the androgen receptor in mouse models, indicating this fungus can reduce PSA levels," Wang said.

"While more research is needed, it's possible that white button mushrooms could one day contribute to the prevention and treatment of prostate cancer."

Thanks.

Kimster