Artemisinin is a natural extract, coming out of a plant called Artemisia annua (sweet wormwood) used as a drug to treat malaria. It saved million of lives so far and as a results, its discoverer Mrs. Tu Youyou received the 2015 Nobel Prize in Physiology or Medicine (Ref.).
Its discovery goes back to 1969. While the whole world was searching a cure for a form of malaria resistant to chloroquine (another element with serious anti cancer potential), Tu, had an idea of screening Chinese herbs. She first investigated the Chinese medical classics in history, visiting practitioners of traditional Chinese medicine all over the country on her own. After screening 2,000 traditional Chinese recipes and made 380 herbal extracts, one compound was effective, i.e. sweet wormwood (Artemisia annua), which was used for “intermittent fevers,” a hallmark of malaria. Here is a complete story of Artemisinin: http://www.cell.com/cell/fulltext/S0092-8674(11)00950-0
Note that, there are various artemisinin derivatives that are also used against malaria, e.g. artesunate and artemether. All are absorbed well after oral intake and cross the blood brain barrier. Artelinic acid, artemether, artemotil (arteether, β-arteether) artenimol (dihydroartemisinin, β-dihydroartemisinin) and artesunate, are considered to be about five times more potent than artemisinin against malaria. (Ref.)
During the past years, Artemisinin has also also been identified as a substance with a strong anti cancer potential in various cancer cells such as
- prostate cancer http://www.ncbi.nlm.nih.gov/pubmed/26655404
- renal cell carcinoma (RCC) http://www.ncbi.nlm.nih.gov/pubmed/26426994
- pancreatic cancer http://www.ncbi.nlm.nih.gov/pubmed/19690861
- gastric cancer http://www.ncbi.nlm.nih.gov/pubmed/23958790
- brain cancer http://www.ncbi.nlm.nih.gov/pubmed/25211298
- liver cancer
- sarcoma http://www.ncbi.nlm.nih.gov/pubmed/24859473
- colorectal cancer: http://www.ncbi.nlm.nih.gov/pubmed/26137537
- endometrial cancer: http://www.ncbi.nlm.nih.gov/pubmed/24296733
- oral squamous cell carcinoma http://ar.iiarjournals.org/content/24/4/2153.full.pdf
- melanoma http://www.ncbi.nlm.nih.gov/pubmed/16273263
- and more http://www.hindawi.com/journals/bmri/2012/247597/tab2/
Artemisinin can be very effective because it selectively affects tumor cells without harming normal cells. This is because Artemisinin affects only cells that contain excessive amounts of iron which is the case for cancer cells. Indeed, via specific receptors cancer cells are demanding and depositing large amounts of Iron as they need it for cellular division. When coming in contact with Iron, Artemisinin triggers the release of intracellular free radicals that destroy cells.
Indeed, Artemisinin was shown to cause the arrest of cell growth and apoptosis in several tumor cell lines. As we will discuss below, besides the ample science behind there is a very large number of anecdotal reports coming from all over the world and supporting Artemisinin and the whole plant Artemisia annua as a cancer solution. For example, Artemisia annua is widely used in countries such as Romania (where they call it “pelin”) or Italy and there are constant positive reports coming out of those countries.
Artemisia annua is a plant that is very cheap and available almost everywhere. This is why people will tend to use the whole plant more than the extract Artemisinin. And this is probably better since the whole plant contains more anticancer substances such as Scopoletin. Recently, it has been reported that Scopoletin can be found in high amounts in Artemisia annua, it it better absorbed in the human body and is known for its cytotoxicity towards cancer cells. (Ref.) Next to Scopoletin there are other substances with anti cancer action as well. (Ref.) As a side note, I was just reading now an article coming to my e-mail box by chance, and indicating that Noni fruit is rich in Scopoletin.
The presence of a complex matrix of chemicals within the leaves of Artemisia annua seems to enhance both the bioavailability and efficacy of artemisinin. In healthy mice, artemisinin serum levels were > 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. On the same line, human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. (Ref.)
This is a good reason to also add a whole plant extract or dried leaves powder next to Artemisinin when considering an anti cancer treatment strategy. And yes, it seems that most of the positive anecdotal reports are coming from the use of the whole plant and not Artemisinin only.
However, when using the whole plant we may get different results. One reason for that can be related to the fact that there are various species that are used depending on the region such as Artemisia absinthium (wormwood), A. annua (sweet wormwood), A. afra (African wormwood), A. capillaries (Korean wormwood), A. vulgaris (common wormwood) and A. asiatica (Asian wormwood). All belong to the same species and enjoy widespread and similar uses in traditional medicine in Africa (A. afra), in Asia (A. asiatica), in China (A. annua), far east (A. capillaries) and Europe (A. absinthium). While the various species above are all expected to have anti cancer effect, I would try to make sure we use A. annua since this is the specie mostly studied in terms of anti cancer effects.
Another point that may lead to various results in various patients is the preparation method of the whole plant extract. This is due to the poor water-solubility of artemisinin which is known since the detection of artemisinin. Youyou Tu, obtained inconsistent antimalarial effects at the beginning as she was extracting the artemisinin in warm water. Only as she went back to the original historical records on the traditional use in Chinese medicine (Handbook of Prescriptions for Emergency Treatment, Hou Bei Ji Fang, by Hong Ge, 281–340 B.C.), she recognized that the press juice rather than hot water extraction was recommended.
Therefore, Artemisinin specifically and Artemisia Annua in general seems to have great anti cancer potential as it acts via a mechanism that is relevant to nearly ALL cancer types. That is by converting cancer cells’s Iron storage in to “bombs”. But the source and administration method of Artemisinin and Artemisia Annua extract matters and it may make the difference in terms of success rate.
Case reports in animals:
Treatment of Iron-Loaded Veterinary Sarcoma by Artemisia annua. http://www.ncbi.nlm.nih.gov/pubmed/24859473
“Artemisinin, a constituent of Artemisia annua L., is a well-known antimalarial drug. Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo. Herbal extracts of A. annua inhibit the growth of cancer cell lines. Here, we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma. The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A. annua. One cat and one dog with fibrosarcoma survived 40 and 37 months, respectively, without tumor relapse. Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months, respectively. A. annua was well tolerated without noticeable side effects. These four cases indicate that A. annua may be a promising herbal drug for cancer therapy. ”
“After the decision was made to use Luparte®, the serum iron (normal range between 140 and 170 µg/dL) was measured. Between blood taking and getting back the serum iron results from the clinical diagnosis laboratory, iron was given p.o. b.i.d or intramuscularly every 3 days to mark the iron affine malignant cells. The initial “blind” dose of orally given iron (e.g. Ferrosanol® capsules 100 mg) was about 100 mg/30 kg b.i.d. or about 100 mg/10 kg weight Ursoferran i.m. two times a week. The iron application was continued for the entire treatment time, and was attuned to maintain the iron level at 250 ± 30 µg/dL. From the fourth day onward, the animals were treated p.o. two to three times daily with one capsule (150 mg in the cat, 450 mg in the dogs) of Herba A. annuae simultaneously.”
Note that the study above used the whole plant Artemisia annua.
Case reports or clinical trials in human:
- A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. http://www.ncbi.nlm.nih.gov/pubmed/26137537
INTERPRETATION: Artesunate has anti-proliferative properties in CRC and is generally well tolerated.
- The dose of artesunate for the study was 200 mg orally, daily for fourteen days, with medication stopped 48–72 h prior to surgery.
- Case Report of a Pituitary Macroadenoma Treated With Artemether http://ict.sagepub.com/content/5/4/391.refs
Artemether was administered orally to the patient over a period of 12 months. Although the tumor remained consistent in size, CT scan shows a reduction in its density, and clinically, the related symptoms and signs resolved significantly as therapy progressed.
- Case report of a laryngeal squamous cell carcinoma treated with artesunate
Artesunate was successfully used in the treatment of laryngeal squamous cell carcinoma and substantially reduced the size of the tumor (by 70%) after two months of treatment.
- On day one of treatment, a capsule containing ferrous sulfate (150 mg) and folic acid (0.5 mg) was given orally at 2:00 PM after a meal. Injections of artesunate (60 mg I.M. per day; Cadila Healthcare Ltd., Ahmedabad, India) were given from day one (01/22/2001) to day 15 (02/05/2001) at 10:00 PM of each day. One tablet of artesunate (50 mg; Cadila Healthcare Ltd., Ahmedabad, India) was taken orally at 10:00 PM after the evening meal every day from day 16 (02/06/2001) onward.
- Artesunate in the treatment of metastatic uveal melanoma–first experiences. http://www.ncbi.nlm.nih.gov/pubmed/16273263
We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months.
Note that the studies above used one component only, i.e. Artesunate, and not the whole plant.
Anecdotal stories in humans:
- inoperable bladder, prostate, ileum and peritoneal in Italy, cured with Artemisinin in combination with Iron (taken 3x/day after meal): http://www.butac.it/artemisia-annua-guadagnare-disperazione/ probably using this Artemisinin source
- in one month, 10×5 tumor reduced to 7×2,5 cm and the disappearance of a large pleural effusion http://www.butac.it/artemisia-annua-guadagnare-disperazione/
- a few successful examples are given in the following patent (Ref.)
- more will be added asap
Artemisinin combats malaria because the malaria parasite collects high iron concentrations as it metabolizes hemoglobin in the blood. Artemisinin contains two oxygen atoms connected together that break down in the presence of iron, by creating very reactive free radicals that kill malaria parasites and cancer cells. Therefore, Iron plays a crucial role in the cytotoxic activities of artemisinin-related endoperoxides through the generation of both ROS and carbon-centred radicals.
Both cancer cells and malaria parasites sequester iron, accumulating as much as 1000 times what normal cells store. In tumors, this is because cancer cells express a high concentration of transferrin receptors on cell surface and have higher iron ion influx than normal cells via transferrin mechanism. Iron is latter required by the cell for DNA replication during cell division. Giving artemisinin to people with malaria or cancer results in destruction of these abnormal cells and leaves normal cells unaffected. This iron-dependent cell death is called ferroptosis. The more cancer cells accumulate Iron the higher the chance for Artemisin therapy to work. Thus, the addition of iron several hours prior to artemisinin administration has been shown to enhance both the cytotoxicity and selectivity of the treatment.
It has been recently suggested that determination of iron-related genes may indicate tumor sensitivity to artemisinins. (Ref.)
Artemisinins usually promote apoptosis rather than necrosis in most of the systems, however in some cases both apoptosis and necrosis have been reported. Induction of apoptosis is a major benefit of artemisinins’ antitumor action as it prevents the collateral effects of inflammation and cell damage caused by necrosis. (Ref.)
Other mechanisms behind Artemisinin compounds: reduction or inhibition of
- phosphoinositide 3-kinase (Ref.)
- Akt (Ref.)
- NF-κB activation (Ref.)
- TNF-alpha (Ref.)
- IL-6 (Ref.)
- HIF1 and VEGF (Ref.)
- and others
Artemisinin has a half-life of about 3-4 hours, Artesunate 40 minutes and Artemether 12 hours. Peak plasma levels occur in 1-2 hours.
Artemisinin compounds inhibit their own absorption. It is possible this occurs more rapidly at higher doses. As a results, discontinuing the use of Artemisinin compounds rapidly (a few days to a couple weeks) returns absorption to normal. Absorption can be reduced by as much as 70 percent with 5-7 days of use (reference needed).
Formulation Source 1: From Wikipedia: its preparation was described in a 1,600-year-old text, in a recipe titled, “Emergency Prescriptions Kept Up One’s Sleeve”. At first, it didn’t work, because they extracted it with traditional boiling water. Tu Youyou discovered that a low-temperature extraction process could be used to isolate an effective antimalarial substance from the plant; Tu says she was influenced by a traditional Chinese herbal medicine source, The Handbook of Prescriptions for Emergency Treatments, written in 340 by Ge Hong, which states that this herb should be steeped in cold water. This book contained the useful reference to the herb: After reading the ancient Chinese medical description, “take one bunch of Qinghao, soak in two sheng (∼0.4 liters) of water, wring it out to obtain the juice and ingest it in its entirety”. (Ref.) After rereading the recipe, Tu realized the hot water had already damaged the active ingredient in the plant; therefore she proposed a method using low-temperature ether to extract the effective compound instead. The animal tests showed it was completely effective in mice and monkeys.
Formulation Source 2: Li’s group also developed suppositories containing artemisinin to treat cerebral malaria that are now being used in field clinics in Africa. Shortening the time to treatment by the use of suppositories improves survival. (Ref.)
Formulation Source 3: Artemisinin is soluble in ethanol (Ref.). Therefore we can use ethanol to extract artemisinin and the other main substances: Add 5g of dried powder into 10ml ethanol and let it stay for 3 days before usage
Administration & Dose:
Reference 1: In Democratic Republic of Congo, 54 malaria-infected volunteers were treated for 10 d with capsules containing powdered leaves of A. annua. Each patient was given 15 g dried leaves containing 15 mg of artemisinin (artemisinin content in leaves = 0.1%). After 2 d all were free of fever and 51 (or 94%) were parasite free after 10 d. (Ref.)
Reference 2: In a study aimed at preventing severe post-operative malaria at Bangui, Central Africa, powdered leaves of A. annua were administered in capsules to 25 patients, 22 of them children aged 1–16 years. Treatment duration ranged from 3–4 d with a dose of 0.4–0.5 g/d of A. annua dried leaves (0.1% artemisinin leaf content) delivering 0.4–0.5 mg/d artemisinin. In spite of the very low administered daily dose of artemisinin, average parasitemia dropped by 62% in the patients with an added benefit of a strong antinociceptive response, especially beneficial to post-operative patients. (Ref.)
Reference 3: artemisinin doses of 1000 mg on day 1 followed by 500 mg on each of days 2–7 that were administered to 227 malaria patients (Ref.)
Diet is an important consideration for any orally delivered drug, and when Dien et al compared artemisinin oral doses given with and without food, Cmax values were similar between subjects who fasted and those who did not. Food consumption along with artemisinin did not seem to affect artemisinin absorption. In contrast, a later rodent study by Weathers et al observed that when artemisinin was consumed as part of a complex plant material, pACT, approximately 45-fold more drug entered the serum of mice than orally administered pure drug. Similarly, when pure artemisinin was fed to mice, it was not detectable in the serum after 60 min. However, artemisinin was detected in the serum when consumed in conjunction with mouse chow, which consists of a variety of plant materials including soy, oats, wheat, alfalfa, beet pulp, corn, etc (Ref.)
Reference 4: The artemisinin content varies from 0.02% to 1.1% of the dry weight.6 Artemisinin and its semisynthetic derivatives are used in antimalarial treatment in artemisinin-based combination therapies, with daily doses between 100 and 200mg (Ref.)
Cotreatment: because of its short half-life, artemisinin requires another drug in combination to obtain a sustained cure against malaria. Indeed, combination therapy has been developed, which is now the standard treatment worldwide. Products that are used in combination with artemisinin, include mefloquine, lumefantrine, piperaquine, and pyronaridine. So combination therapies used today are:
Summary from literature:
- Artemisinin is administrated at 500 to 1000mg/day
- Whole plant is better then artemisinin capsules in terms of reaching a specific level in blood even if the whole plant contains much much lower amount of artemisinin
- Whole plant tea infusion leads to shorter half life and needs to be administrated 4x/day (Ref.)
- Whole plant dried leaves better then tea infusion, but tea infusion better then pure artemisinin (Ref.)
- Dried leaves of the plant may be better and up to 15g/day of dried lives were administrated to patients for at least 10 days. In another study 0.5g/day was administrated to patients and was still effective. In yet another study 2–5 tablets of 500mg dried leves, twice on day 1, followed by 1–4 tablets twice daily for the next 5 d was administrated and effective anti malaria (Ref.)
- The whole plant seems to work best when administrated with or after meal (Ref.)
Main conclusions on administration and dose:
- Oral consumption of A. annua dried leaves capsules is more effective than the pure drug. (Ref.1, Ref.2, Ref.3, Ref.4)
- it can be found as whole plant or capsules online (or grown at home)
- used dose of dried leaves powder is from 0.5g/day up to 15g/day; I would start with o.5g/day and increase the dosage to about 5g/day (Ref.)
- administrated during or after meal
- divide the daily dose in two or more administrations
- Artemisnin compounds inhibit their own absorption. Discontinuing the use of Artemisnin compounds rapidly returns absorption to normal. As a result it is better to stop administration of Artemisinin compounds during the weekend.
- Oral consumption of A. annua dried leaves in hot water
- dried lives can be boiled in hot water
- 5g/day of dried leaves (or 25g of fresh leaves) (Ref.)
- drank throughout the day
- the disadvantage is that its taste is bitter
- also the disadvantage is that is may be less effective compared to the dried leaves administrated as capsules
- Oral consumption of A. annua dried leaves in cold water or ethanol
- I need to clarify more this formulation as it may be very relevant
- I need to clarify more this formulation as it may be very relevant
- Oral consumption of Artemisinin or others derivatives is less effective compared to dried leaves but still used by many
- can be found as capsules online
- used doses from 2 mg/kg/day and higher; usually is taken at 100mg/day up to 1000mg/day
- usually administrated 30 min before food – the common belief is that it needs to be taken on an empty stomach as the iron in food will react with the Artemisinin compounds – however most clinical trials and the anecdotal reports suggesting response were administrating with or after the meal
- best to combine Artemisinin, Artesunate and Artemether
- divide the daily dose in two administrations
- Artemisnin compounds inhibit their own absorption. Discontinuing the use of Artemisnin compounds rapidly returns absorption to normal. As a result it is better to stop administration of Artemisinin compounds during the weekend.
- IV administration
- Typically administrated as Artesunate, a few times/week
- usually daily dose is 300mg or 5mg/kg/day
- administrated in 250ml NaCl solution during about one hour
(IV administration is based on best practices at German clinics)
- Avoid using glutathione supplements or other strong anti oxidants such as NAC as they may cancel out the pro-oxidant anti cancer effect of Artemisinin compounds
The belief is that
- administrating Iron supplements a few days prior and during artemisinin treatment will enhance the effectiveness of the therapy (for safety reasons I would make sure there are some hours in between Iron administration and Artemisinin)
- combining with Sodium Butyrate at about 3g/day dose may enhance the effectiveness of Artemisinin compounds. Sodium Butyrate is a substance with its own anti cancer effects and can be found as a supplement online.
- vitamin C taken after breakfast and after lunch, enhances the iron absorption from the stomach so that Iron will reach the tumor prior to artemisinin administration
- it is not recommended to use concurrent with radiation therapy due to damage to healthy cells from iron leakage from dying cancer cells
In more than 4000 case studies, no significant toxicity from artemisinin has been found, which makes it far different than conventional chemotherapy.
It is not recommended to use concurrent with radiation therapy due to damage to healthy cells from iron leakage from dying cancer cells
In short term studies of single agent artesunate 8 mg/kg/day in normals, altered taste and slight decrease in reticulocyte count were the only side effects noted. (Ref.)
It may lead to slight decrease of Hemoglobin during teh treatment. Therefore monitoring hemoglobin is advised (Ref.)
Experimental studies showed additive or synergistic activities with antineoplastics, antibiotics, antifungals, sodium butyrate, and chloroquine, where it could become more effective in fever subsidence and disappearance of malarial symptoms. (Ref.)
Other interactions and synergies: http://www.hindawi.com/journals/bmri/2012/247597/tab3/
Source and Price:
Artemisia annua – whole plant extract – oral capsules:
- e.g. Artecin (500mg/capsule), Italian product (600mg/capsule), Arthrem
However, I think the best is to buy the powder and make our own capsules so that we know exactly what is inside (see below source for the whole plant powder)
Artemisinin oral capsules:
- one of the best source based on chemosensitivity test I saw is Super Artemisinin which is sold by e.g. Nutricology and Allergy Research. This also contains oil extract from teh leaves.
- one of the only source I know combining Artesunate & Artemisinin & Artemether is Artemix http://www.hepalin.com/artemix.htm
- it costs about 50 euro a vial of 250 to 300mg. One source is Burg Apotheke
Seeds to grow Artemisia
- a lady from Germany expert in growing Artemisia (Ref.)
Dried whole plant
- plant https://www.borreliose-karde.de/de/beifuss-einjaehrig-tee-100g-artemisia-annua.html
- powder http://www.teemana.de/de/preisliste.html (I recently ordered this product and will check my experience – the plant seems to be grown in Germany)
Artemisinin should be kept in a well-closed container, protected from light and stored in a cool place.
BACKGROUND: Artemisia annua L, artemisinin and artesunate reveal profound activity not only against malaria, but also against cancer in vivo and clinical trials. Longitudinal observations on the efficacy of A. annua in patients are, however missing as of yet.
METHODS: Clinical diagnosis was performed by imaging techniques (MRT, scintigraphy, SPECT/CT) and blood examinations of standard parameters from clinical chemistry. Immunohistochemistry of formalin-fixed, paraffin-embedded tumor material was performed to determine the expression of several biomarkers (cycloxygenase-2 (COX2), epidermal growth factor receptor (EGFR), glutathione S-transferase P1 (GSTP1), Ki-67, MYC, oxidized low density lipoprotein (lectin-like) receptor 1 (LOX1), p53, P-glycoprotein, transferrin receptor (TFR, CD71), vascular endothelial growth factor (VEGF), von Willebrand factor (CD31)). The immunohistochemical expression has been compared with the microarray-based mRNA expression of these markers in two prostate carcinoma cell lines (PC-3, DU-145).
RESULTS: A patient with prostate carcinoma (pT3bN1M1, Gleason score 8 (4+4)) presented with a prostate specific antigen (PSA) level >800 µg/l. After short-term treatment with bacalitumide (50 mg/d for 14 days) and long-term oral treatment with A. annua capsules (continuously 5 × 50 mg/d), the PSA level dropped down to 0.98 µg/l. MRT, scintigraphy and SPECT/CT verified tumor remission. Seven months later, PSA and ostase levels increased, indicating tumor recurrence and skeletal metastases. Substituting A. annua capsules by artesunate injections (2 × 150 mg twice weekly i.v.) did not prohibit tumor recurrence. PSA and ostase levels rose to 1245 µg/l and 434 U/l, respectively, and MRT revealed progressive skeletal metastases, indicating that the tumor acquired resistance. The high expression of MYC, TFR, and VEGFC in the patient biopsy corresponded with high expression of these markers in the artemisinin-sensitive PC-3 cells compared to artemisinin-resistant DU-145 cells.
CONCLUSION: Long-term treatment with A. annua capsules combined with short-term bicalitumide treatment resulted in considerable regression of advanced metastasized prostate carcinoma. Controlled clinical trials are required to evaluate the clinical benefit of A. annua in prostate cancer.
From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. https://www.ncbi.nlm.nih.gov/pubmed/28254675
Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against tumors. The cellular response of ARS and its derivatives (dihydroartemisinin, artesunate, artemether, arteether) towards cancer cells include oxidative stress response by reactive oxygen species and nitric oxide, DNA damage and repair (base excision repair, homologous recombination, non-homologous end-joining), various cell death modes (apoptosis, autophagy, ferroptosis, necrosis, necroptosis, oncosis), inhibition of angiogenesis and tumor-related signal transduction pathways (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, and others) and signal transducers (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc). ARS-type drugs are at the stairways to the clinics. Several published case reports and pilot phase I/II trials indicate clinical anticancer activity of these compounds. Because of unexpected cases of hepatotoxicity, combinations of ARS-type drugs with complementary and alternative medicines are not recommended, until controlled clinical trials will prove the safety of non-approved combination treatments.
Cancer combination therapies with artemisinin-type drugs http://www.sciencedirect.com/science/article/pii/S0006295217301818
Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then probably as part of combination therapy regimens rather than as monotherapy. In the present review, I give a comprehensive overview on synergistic and additive effects of artemisinin-type drugs in combination with different types of cytotoxic agents and treatment modalities: (a) standard chemotherapeutic drugs, (b) radiotherapy and photodynamic therapy, (c) established drugs for other indications than cancer, (d) novel synthetic compounds, (e) natural products and natural product derivatives, (f) therapeutic antibodies and recombinant proteins, and (g) RNA interference. I also summarize the activity of artemisinin-type drugs towards multidrug-resistant cells and tumor cells with other drug resistance phenomena. As synergistic interactions may not only occur in tumor cells, toxic reactions in normal cells (hepatotoxicity, drug interactions) were also considered. This review summarizes the scientific literature of more than 20 years until the end of 2016.
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