A complete overview of artesunate and the cancer relationship.
1. From Malaria to Babesia to Cancer
Artemisinin is an active ingredient extracted from Chinese herbal medicine Qing Hao (Herba Artemisiae annuae), a sweet wormwood plant. Artemisinin and its molecule-modified derivatives, such as artesunate are first used as anti-malaria medication and now found they are also potent anti-cancer remedies.
(Efferth T, et al., 2001) World Health Organization has recommended them as the first line anti-malaria treatment. Millions of cases have been treated with these substances and the cure rate was very high and fast. It is very effective for drug-resistant malaria. Articles are available documenting the extensive pre-clinical and clinical testing that has been done. (Bharel S, et al., 1996, Gulati A et al., 1996)
In Zhang’s Clinic, we are using molecularly modified artemisinin derivative artesunate to treat babesiosis, a co-infection of Lyme disease, which is a malaria-like protozoa infection of the red blood cells. Recently we also use it as a non-toxic, gentle, and adjunctive treatment for cancers. Since it is effective in both anti-babesiosis and anti-cancer treatments, we did literature research and the results are reviewed in this article.
2. Pre-Clinical Studies— Anti-Malaria, -Babesia, and -Cancer Mechanism
The mechanism of artemisinin and its derivatives anti-malaria and babesia protozoa actions is speculated to be related to the iron metabolism of the protozoa. Its molecular peroxide group produces reactive oxygen atom, which can interfere with the iron metabolism of the protozoa. Similarly, iron is required for cell division and many cancer cells aggressively accumulate iron for their rapid cell division.
Therefore the artemisinin and its derivatives can react with the iron within the cancer cells to interfere with their division and to push them to enter apoptosis (Schaller J, 2006). Artemisinin has been shown to work through oxygen and carbon-based free radical mechanisms. Its structure includes an endoperoxide bridge.
Peroxides generate free radicals in a Fenton type reaction when exposed to unbound ferrous iron. Malaria and babesia, which grow in the erythrocytes, have the opportunity to accumulate much excess iron, which can spill into the unbound form. Electron microscopy has confirmed the destruction of plasmodium membranes with morphology typical of free radical mechanisms.
With the knowledge of a high accumulation of iron in cancer cells, researchers Henry Lai and Narenda Singh of the University of Washington became interested in possible artemisinin activity against malignant cells. In 1995, they published a paper in Cancer Letters concerning the use of artemisinin against numerous cancer cell lines in vitro. This article has mobilized interest in artemisinin as an addition to anticancer treatment (Lai H et al., 1995).
They further confirmed this mechanism and reported that artemisinin-tagged holotransferrin can enhance the selective cancer cell killing effects of artemisinin and were not toxic to the normal cells. They found that tagging artemisinin to transferrin, both iron and artemisinin would be transported into cancer cells in one package.
Once inside a cell, iron is released and can readily react with artemisinin close by tagged to the transferrin. This would enhance the toxicity and selectivity of artemisinin towards cancer cells. They then tested the compound on a human leukemia cell line (Molt-4) and normal human lymphocytes.
They found that holotransferrin-tagged artemisinin was very potent and selective in killing cancer cells but not hurting the normal cells. Thus they concluded that the ‘tagged-compound’ could potentially be developed into an effective chemotherapeutic agent for cancer treatment (Lai H et al., 2005).
Another anti-cancer effect of artemisinin and its derivatives is that they promote the cancer cells to enter apoptosis. The effect could be enhanced by increasing the iron contains in the cancer cells. Singh NP et al., reported that cancer cell line Molt-4 cells were first incubated with 12 microM of human holotransferrin to enhance the iron supply to the cells.
The cells were then pelleted and transferred to a culture media contains 200 microM of a derivative of artemisinnin, dihydroartemisinin (DHA) and incubated. They found that DHA treatment significantly decreased cell counts and increased the proportion of apoptosis in cancer cells compared to controls (chi2=4.5, df=l, p<0.035).
The addition of holotransferrin significantly further decreased cell counts (chi2=4.5, df-l, p<0.035) and increased apoptosis (chi2=4.5, df=1, p<0.035). No necrotic cells were observed. They concluded that the rapid induction of apoptosis in cancer cells after treatment with DHA indicates that artemisinin and its derivatives may be effective anti-cancer agents (Singh Np et al., 2004).
These mechanisms have commonly existed in many types of cancers, therefore, its anti-cancer spectrum is wide. One of the derivatives, deoxyartemisitene has been tested to have the effects to suppress 14 different human cancer cell lines. (Galal AM, et al., 2002) The following cancers have the highest sensitivity to these substances: leukemia, colon cancer, and melanoma (Berger TG et al., 2005, Efferth T, et al., 2002).
It has also shown suppression effects on the following cancers: breast cancer, ovarian cancer, prostate cancer, brain cancer, kidney cancer, and others. (Efferth T, et al., 2006, Anfosso L, et al., 2006, Paik IH, et al., 2006, Galal AM, et al., 2002, Lee CH, et al., 2000, Singh NP, et al., 2001) The similar anti-cancer activities have also been found in other derivatives of artemisinin, such as arteether, artemether, dihydroartemisinin (Singh NP, et al., 2001).
In the cell culture of drug-resistant breast cancer found that they have high propensity of iron accumulation. When these iron-loaded cells were treated with artemisinin, 75% of them die within eight hours, and nearly 100% die within 24 hours. But the control normal cell culture, which has no heavy iron load, was not affected (Singh NP, et al., 2001, Lai H, et al., 1995).
The combination of the existing of both iron and the artemisinin or its derivatives is required to suppress cancer cells. This has been studied by animal studies. (Moore JC, et al., 1995) So it is believed that the main mechanism of cancer-suppressing effects of artemisinin and its derivatives is that the peroxide-oxygen spark that occurs inside the cancer cell seems to be the most convincing theory (Schaller J, 2006, Efferth T. et al., 2006).
If we can increase the cellular iron load, such as using holotransferrin to increase the intracellular iron level, then the efficacy of the cancer treatment by these derivatives, especially by dihydroartemisinin can be enhanced (Singh NP, et al., 2001). Another possible mechanism is that these substances can combine and alter their functions of certain proteins unique to those cancers. (Lee CH, et al., 2000) These effects work together to cause the cancer cell to enter apoptosis and die (Singh NP, et al., 2004).
Artesunate is a semi-synthetic derivative of artemisinin, and has been analyzed for its anti-cancer activity. It is against 55 cancer cell lines reported by the Developmental Therapeutics Program of the National Cancer Institute, USA. (Efferth et al., 2001) It has dramatic cytotoxic activity against a wide variety of cancers including drug resistant cell lines. Artesunate was most active against leukemia and colon cancer cell lines. Mean growth inhibition 50% (GI50) 1.11microM and 2.13 microM respectively.
Non-small cell lung cancer cell lines showed the highest mean (GI50 26.62 microM) indicating the lowest sensitivity towards artesunate. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. Most important, a comparison of artesunate’s cytotoxicity with those standard cytostatic drugs showed that artesunate was active in molar ranges comparable to those of established anti-tumor drugs.
Leukemia lines resistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea were tested. Remarkably, none of these drug resistant lines showed resistance to artesunate. The theorized reason for this is the absence of a tertiary amine in artesunate, present in virtually all other chemotherapy agents, which is required for cellular transport systems to usher the drug outside the cell (Rowen R, 2002). Compare with artemisinin, artesunate is much more effective and less adverse reactions, so our clinic uses only artesunate as the main ingredient in our herbal supplement product Artemisia Capsule.
Cancer cells are deficient in antioxidant enzyme superoxide dismutase. The manganese form in mitochondria and the copper zinc form in the cell cytoplasm are generally low in cancer cells. Cancer cells are grossly deficient in catalase and glutathione peroxidase, both of which degrade hydrogen peroxide.
It is these deficiencies in antioxidant enzymes, which lead to the use of many of the common chemotherapeutics that are superoxide generators. The higher iron fluxes, especially associated with the mitosis phase of cancer cells, should render these cells more susceptible to oxidative damage via hydrogen peroxide and superoxides.
Normally, the profound catalase deficiency in cancer cells is credited with creating vulnerability to oxidants. However, since all of these protective antioxidant enzymes are most often deficient in transformed cells, the oxidant vulnerability should be enhanced dramatically due to enhanced unbound iron during cell division. This is the anti-cancer mechanism of artemisinin and its derivatives (Levine SA, et al.,1985).
3. Clinical Observations
Clinically, Dr. NP Singh has been following a series of cancer patients with nearly universal improvement on artemisinin or its derivatives. He believes artemisinin will prove to be the most powerful, yet extremely inexpensive and safe chemotherapeutic agent yet found and effective orally for home use. He emphasizes that it should be used in professional medical settings together with complementary strategies employing detoxification, diet, immune support, spiritual work, etc. The Dr. Hoang family has observed a 50-60% long-term remission in over 400 cancer patients utilizing artemisinin together with a comprehensive cancer strategy, and with no observed toxicity (Rowen R, 2002).
In Zhang’s clinic we have been using the Artemisia Capsule in which the main ingredient is artesunate treating pre-cancerous conditions and found that it can turn several pre-cancerous conditions to normal. Two cases of biopsy-confirmed stomach intestinal epithelium metaplasia, which is a pre-cancerous condition of stomach cancer, treated with Artemisia Capsule (contains artesunate 33.3 mg per capsule) three times a day for two months.
Repeated GI biopsy found the metaplasia disappeared. We have been using the ingredient of this capsule together with allicin solution to do vaginal suppository for patients diagnosed with cervical dysplasia by PAP smear. This treatment has been making every case to turn the dysplasia to negative in follow up PAP smear within a few weeks time.
For patients already diagnosed with cancer or already finished conventional oncology treatments. We have use the Artemisia Capsule as secondary prevention and complementary treatments for the elimination of possible residual cancer cells to prevent relapse and metastasis. We have seen promising results in treating hepatocellular carcinoma, breast cancer, lymphoma, multimylenoma, urine bladder cancer, and oral cancers.
In those patients who had their main lesion being treated but still have untreated scatter cancer lesions, the artesunate treatment could not totally eradicate the tumors but made them shrunk and stabilized. It could turn cancer to be a chronic manageable disease. For those patients have their main cancer lesions removed either by surgery, chemotherapy, or radiotherapy, the artesunate treatment preventing them from relapse and metastasis. Combined with Chinese herbal treatments, we have been greatly improving the life quality and long-term outcome of cancer treatments.
Artemisinin and its derivatives, such as artesunate, have been clinically used for treating the following common cancers.
Hepatocellular Carcinoma (Liver Cancer):
Our clinic has been treating many patients with viral hepatitis B and C. In their advanced stages, they risk to have hepatocellular carcinoma (HCC). Therefore we have been treating a number of cases of HCC patients. We use Artemisia Capsule in which artesunate is the main ingredient as the major remedy.
In these patients some have their lesion being treated by surgery or embolism and alcohol or radio-frequency ablation. But none of them have their all lesions being totally removed with those treatments. When they came to see us all have certain untreated HCC lesions in their liver.
After the artesunate treatment, their lesion becomes stabilized and some scatter small lesions disappeared. The treatment also includes liver function restoration and liver inflammation control. Now all our HCC patients are surviving much longer than their expected survival time and enjoying their better life quality. The following is two cases stories:
Case 1. Fran was 73 when she visited Zhang’s Clinic on Dec. 14, 2000, with a diagnosis of HCC and hepatitis C that was already in the decompensated cirrhosis stage. She had light jaundice, gallstones, elevated ammonia (69.8), leukopenia (WBC 2.3), anemia, low platelets (60), mild ascites, and edema, liver inflammation, and bile retention.
She also had an enlarged spleen consistent with portal vein hypertension. Besides the liver condition, she also had type II diabetes. She has severe fatigue and insomnia. Following an MRI performed on Nov. 8, 2000, found two lesions on her liver: one high in segment 8 measuring 2.9 x 3.0 cm; the other in segment 6, which was slightly exophytic, measured 3.7 x 3.4 cm.
She was treated at the Sloan – Kettering Institute with embolism on both lesions and alcohol ablation on the lower lesion. The higher one was left alone without ablation, because it was too close to the lung and Fran was too weak to tolerate ablation for both lesions. As the hospital could offer no further treatment, She visited Zhang’s Clinic for Chinese herbal treatment.
Dr. Zhang concentrated on restoring her liver function with hepatitis C protocols and anti-cancer herbal formula R-6532 Capsule, which was a modified formula of Kang Ai Bao (CJITWM, 1997, 17(12):730-732). Within three months, Fran’s liver function had improved. Jaundice and ascites disappeared, the ammonia level normalized, and the edema released. A CAT scan was done on July 19, 2001, revealed that the size of the higher lesion had shrunk to 1.1 cm (from 2.9 x 3.0 cm) and the lower lesion had shrunk to 2.7 x 2.3 cm. (from 3.7 x 3.4 cm).
No new lesion was seen. Thereafter, every half year, a CAT scan was done to monitor the HCC lesions. On Dec. 18, 2003, there were new lesions discovered in segment 7 and 6 with suspicious activity. Then Fran’s general health and liver function were good enough to perform an embolism and alcohol ablation. These procedures were successfully completed. Thereafter we add artesunate (Artemisia Capsule) in her protocol to enhance the anti-cancer effects. Currently, she is monitored once every six months because the lesions are stable and her quality of life is fairly good.
When this article is writing Fran now is 81 and continuing the herbal regimen. She enjoys a normal life despite her compromised liver function eight years after her HCC diagnosis.
Case 2. Margaret N. 58 visited Zhang’s Clinic four months after the liver resection surgery on September 16, 2003. Her hepatocellular carcinoma (HCC) was diagnosed in May 2003. Long-term taking estrogen-based birth-control pills possibly caused her HCC. After conventional oncology treatment finished and no further treatment was suggested to her.
At diagnosis, there was a big tumor of 8.5 cm in segment 5 and 6. A few small lesions in segment 8 and also a tumor size 2.2 X 1.6 cm in segment 2, All lesions were in the right lobe of the liver. The big tumor was removed by liver resection. After surgery, there was no chemotherapy or radiotherapy to follow.
The lesion in the segment 2 was treated by radiofrequency ablation. Small lesions in segment 8 were not treated. This was her tumor status when she visited Zhang’s Clinic. Blood tests showed that her AFP was 12 after surgery. AKP was raised and ALT, and GGT were normal but AST was mildly elevated. She complaint liver area discomfort but otherwise felt okay.
Since her cancer load was greatly reduced by surgery and radiofrequency ablation. We started herbal anti-cancer treatment by using formula R-6532, which is a formula for after oncology treatment patients. At the same time, we use liver protective herbal formula Hepa F. #2 Capsule to restore her liver function.
Cordyceps capsule to improve her cellular immunity and Circulation P Capsule to improve her blood rheology and microcirculation. Ten months on this protocol she felt well and all her liver functions were in the normal range, but slightly elevated AST and AKP. AFP dropped from 12 to 3.4. On April 5, 2004, about one year after the surgery and seven months on herbal treatment, an MRI has done and compared with the MRI done right before the herbal treatment on 9/17/03.
The findings of this comparison read: The patient is status post resection of hepatic segments 5 and 6, cholecystectomy and radiofrequency ablation of a lesion in segment 2. A hypervascular lesion in hepatic segment 8 is stable. Other previously noted smaller lesions in right hepatic lobe are no longer seen.
The lesion in segment 2 has decreased in size from 2.2×1.6 cm to 1.8×1.6 cm. …. Impression: Since 9/17/03,
- A stable lesion in hepatic segment 8.
- Previously noted smaller lesions in the right hepatic lobe are no longer seen.
- Decrease in size of a lesion in hepatic segment 2.
At this time we added Artemisia Capsule, which contains the main ingredient artesunate. One year later, on April 29 2005 MRI was done to compare with MRI done on 10/4/04 and 4/5/04. found that the lesion at segment 2 further reduced the size to 1.4×1.2 and previous hyperintense foci scattered throughout the liver are not clearly seen.
Her liver function tests were all normal. She has yearly check-ups with MRI and later scans found her liver lesion was stable and no new lesion development. It is possible that her lesion showed on the MRI might already become scar tissues.
The Chinese medicine treatment was non-toxic and complementary to the western medical treatments. The Zhang clinic has been treating more than 10 HCC patients who have been living with stabilized HCC lesions for up to three years or longer with similar herbal medicine protocols. All have exceeded their expected survival times following HCC diagnosis, all are still carrying stabilized HCC lesions, and all report improved quality of life with herbal treatment.
Liu Y, et al., and Sun WC, et al., studied to combine artemisinin and its derivatives with large carbon molecule, such as lipophilic alkyl carbon chains, which can dramatically enhance its anti HCC effects. With the large carbon chain the HCC cell killing effects of these artemisinin derivatives being strengthened 200 times. (Liu Y, et al., 2005, Sun WC, et al., 1992)
Breast Cancer:
For breast cancer, Lai H, et al., found that in rats the chemically induced breast cancer can be prevented or treated by Artemisinin. They fed the food to the rats containing 0.02% of artemisinin for 40 weeks and found only 43% of the rats developed cancer compared to 96% of the rats in control group developed cancer without the artemisinin treatment. (Lai H, et al., 2006) Singh NP, et al., treated human breast cancer cell with holotransferrin and dihydroaremisinin together and found that this combination can kill a type of radiation-resistant human breast cancer cells but it has no effects on the normal human breast cells (Singh NP, et al., 2001).
In our clinic, we use artesunate based Artemisia capsule for breast cancer patients for their prevention of recurrences and metastasis after surgery, chemo or radiation treatments. We have used this method for many years and up to now there was no one case had recurrence or metastasis reported. A case history reported by Townsend Letter for Doctors & Patients reads: Patient D.E., a 47-year-old Alaska resident with stage 4 breast cancer and metastases to vertebral T1 with significant pain, vertebral collapse and local neurological impairment.
First seen May 2001, she received a series of IPT (insulin potentiation therapy-low dose chemotherapy), high dose vitamin C infusions, supplements, and dendritic cell vaccine, dietary management, and detoxification strategies. Most symptoms had cleared within 4 months (October 2001). In January 2002, she received artesunate IV (source: mainland China), plus oral artemisinin 300 mg twice a day, which has been continued. Six months later she was happy to report she has no symptoms whatsoever and is living a normal life. Her local provider believes the regressed mass is now scar tissue (Rowen R, 2002).
Even for widely metastatic breast cancer these substances combined with other alternative supplements got very satisfying results and another such case report reads: L.L. is a West Coast woman in her 40’s with breast cancer and extremely painful bone metastases all over her spine. She had received limited radiation therapy to reduce the pain in the thoracic spine. She began artemisinin, and a variety of complementary strategies, including diet, detoxification, and Kelly type proteolytic enzymes. Immediately, her energy exploded.
Her pain level took a dive. Her comment after two weeks on artemisinin was “Last week I thought I was dying, and today for the first time in months, I believe I am going to live.” Four months into therapy using oral supplements, diet and detoxification strategies, a PET scan, the most efficient and sensitive study for the spread of cancer, did not show any activity anywhere in her spine, even in places that were present before and not radiated. Further, the scan did not confirm definite cancer activity anywhere else. (Rowen R, 2002).
Cervical Cancer:
Cervical cancer is caused by human papilloma virus (HPV) infection and now there is a vaccine available to prevent it. Since cervical cancer cells have large numbers of transferrin receptor to increase their iron uptake, therefore, artemisinin and it derivatives, such as artesunate and dihyroartemisinin (DHA) showed strong effects to cervical cancer cells and they do not injury normal cervical tissue.
Disbrow GL, et al., reported that when used topically in animal studies, they found that apply DHA in the cervical areas of dogs and then exposed to the HPV DHA strongly inhibited HPV induced cancer development (Disbrow GL., et al, 2005). In Zhang’s Clinic, we use artesunate and Allicin mixture as a vaginal suppository to treat cervical dysplasia and every case got their PAP smear turned to normal within a few weeks.
Leukemia and Lymphoma:
Singh NP et al. reported that when artemisinin and sodium butyrate used together can dramatically enhance artemisinin’s suppressive effects on leukemia cells. This combination does not harm normal white blood cells and lymphocyte. These two substances have synergetic effects to each other. When used separately, artemisinin and butyrate can only suppress 40% and 32% of the leukemia cells respectively.
When they are used together, 100% of the leukemia cells were killed within one day. (Singh NP, et al., 2005) In Zhang’s clinic, we have been using Artemisia Capsule in which the main ingredient is artesunate for chronic lymphocyte leukemia and keeping patients blood counts and clinical condition stable.
A case history from the Townsend Letter for Doctors & Patients reported：Patient D.A. a 47 year-old mechanic who presented with a 4.5 cm. Non-Hodgkin’s lymphoma on the right side of his head, with a gaping incision from a recent biopsy, and tremendous inflammatory erythema.
Artesunate, 60mg was injected muscularly 14 consecutive days and he switched diets to high protein/vegetable (Kelley parasympathetic type diet). At the end of two weeks, a depression appeared at the apex of the tumor. Four weeks later, the mass was completely gone, skull surface smooth, incision totally healed and erythema virtually cleared. Apparently he is cancer-free as of this writing 6 months later (Rowen R, 2002).
Melanoma and Skin Cancer:
Berger TG., et al., reported their experience of treating metastatic melanoma case with artemisinin. The patient had metastatic melanoma and failed to respond to conventional chemotherapy. After using artemisinin her cancer was stabilized at first and then found her metastatic lesions in the lung and spleen regressed.
This patient is still alive four years after the advanced melanoma was diagnosed. The expectation of life of this kind of cancer is usually less than a few months (Berger TG, et al., 2005). For skin cancer artemisinin and its derivatives can be used as a topical application and the results were very satisfactory.
A case reported the use of artesunate mix with DMSO applied topically and cured the skin cancer lesion within a short period of time and the case report reads Patient F.A., an 81-year-old Californian with multiple skin cancers including one active recurrent quarter-sized lesion that had been burned 4 times previously. Topical artemisinin (artemisinin in 50% DMSO) applied twice daily caused the large lesion to fall off within 5 days and other smaller skin cancers to regress. His wife reported the same with her skin cancers (Rowen R, 2002).
Glioma:
The brain tumor is not sensitive to chemotherapy and conventional treatment mainly is radiation. Kim SJ et al., found that when using dihyroartemisinin (DHA) together with the radiation, the glioma cells become more sensitive to the radiation. They found that when the glioma cell culture was treated with DHA, the number of cell colonies reduced and when radiation is given together with the DHA treatment, the reduction of the colonies even much more.
In their study, they also found that when antioxidant used the effects of DHA was blocked. Therefore during the DHA treatment, free radical scavengers or antioxidants should not be used. (Kim SJ, et al, 2006)
Other Cancers:
Some other cancers have also been studied to respond to the artemisinin and its derivatives treatments. They are stomach cancer (Sun WC, et al., 1992), small-cell lung cancer (Sadava D, et al., 2002), ovarian cancer (Chen HH, et al., 2003), oral squamous cell carcinoma (Yamachika E, et al.,2004), fibrosarcoma (Moore JC, et al., 1995), astrocytoma (Efferth T, et al., 2004), Kaposi’s sarconma (Dell’Eva R, et al., 2004), Prostate Cancer, Posner GH et al., reported that artemisinin derivatives had strong suppressive effects on prostate cancer. (Posner GH, et al., 1999, 2004) and non-small cell lung cancer… etc. Non-small cell lung cancer: A case reported by Townsend Letter for Doctors & Patients reads: Patient V.M. an 83-year-old Toronto resident.
Healthy most of her life, she now had a non-small cell lung carcinoma in the right lower lobe, considered non-resectable because of heart failure and circulatory problems. She received artemisinin 500mg twice a day and Carnivora oral, via nebulizer, 5cc twice a day. In 4 months the tumor shrunk to 1×2 cm and her oncologist felt this represented scar tissue and declared her cancer-free. Her heart condition improved considerably with CoQ10, 600mg daily (Rowen R, 2002).
4. Summary
Artemisinin and its derivatives have been used for treating malaria for decades and have treated millions of patients. The effects were extremely good and fast. They have been recommended as a first-line anti-malaria treatment by WHO. Because of the similarity of babesia infection and malaria, we have been using it for treating babesiosis, the common co-infection of Lyme disease. Especially its molecular modified derivative artesunate, which is more potent and fewer side effects than artemisinin has been used in our clinic mainly for treating babesiosis and found that its efficacy was much better than conventional medications.
The mechanism of cancer cells division and the protozoa of malaria and babesia replication are both involved with the oxidation and reduction of the iron. Artemisinin and its derivative can selectively interfere this mechanism. Since 1995 researchers in the University of Washington started its anti-cancer studies. Pre-clinical and clinical studies found artemisinin and its derivatives are potent anti-cancer substances with no obvious toxicity in therapeutic dosage and very inexpensive compared with most chemotherapy drugs.
It is selectively effective on the cancer cells without damage the normal cells. This is an ideal anti-cancer treatment, especially for the development of humane, gentle cancer care methods. Because it is non-toxic and it has very wide anti-cancer spectrum so it could be used right after a cancer diagnosis to prepare the patient for further oncology treatments.
It could also be used after surgery, chemo, or radiation to prevent relapse and metastasis as secondary prevention. Its non-cytotoxic mechanism of anti-cancer could open a brand new field of anti-cancer research and made the development of non-toxic anti-cancer treatment possible.
References:
Anfosso L., et al., Microarray expression profiles of angionenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J. 6:269-78, 2006
Berger TG, et al., Artesunate in the treatment of metastatic uveal melanoma – first experiences, Oncol Rep. 2005; 14:1599-603
Bharel S, Gulati M, Abdin P, Srivastava S. Structure biosynthesis and functions of artemisinin. Fitoterapia Vol LXVII No 5, l996.
Chen HH, et al., Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro.” Pharmacol Res 48: 231-236, 2003.
Dell’Eva R, et al., Inhibition of angiogenesis in vivo and growth of Kaposi’s sarcoma xenograft tumors by the anti-malaria artesunate. Bio-chem Pharmocol. 68:2359-66, 2004
Disbrow GL, et al., Dihyroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo. Cancer Res. 65:10854-61, 2005
Efferth T, Dunstan H, Sauerbrey A, et al: The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767-773, 2001.
Efferth T, Olbrich A, Bauer R: mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether. Biochem Pharmacol 64:617-623, 2002.
Efferth T, et al., Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radic Bio Med. 37:998-1009, 2004
Efferth T., et al., Molecular pharmacology and pharmcogenomics of artemisinin and its derivatives in cancer cells. Curr Drug Targets, 7:407-21, 2006
Galal AM, et al., Deoxyartemisinin derivatives from photooxygenation of anhydrodeoxydihydroartemisinin and their cytotoxic evaluation. J. Nat Prod. 65:184-8, 2002
Gulati A, Bharel S, Srivastava M, Abdin MZ. Experimental Studies on Artemisia, an herbal remedy for malaria. Fitoterapia Vol LXV11 No 5, 1996.
Kim SJ, et al., Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J. Cancer Res Clin Oncol. 132:1`29-35, 2006
Lai H, Singh NP: Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Lett 91:41-46, 1995.
Lai, H., et al., Effects of artemisinin-tagged holotransferrin on cancer cells. Life Sciences, 2005 (Vol. 76) (No. 11) 1267-1279
Lai H, et al., Oral artemisinin prevents and delays the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in the rat, Cancer Latt, 231:43-8, 2006
Lee CH, Hong H, Shin J, et al.: NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin. Biochem Biophys Res Comm 274:359-369, 2000.
Levine SA, Kidd PM. Antioxidant Adaptation: Its Role in Free Radical Pathology. Allergy Research Group, San Leandro, California, 1985.
Liu Y, et al., Synthesis and cytotoxicity studies of artemisinin derivatives containing lipophilic alkyl carbon chains. Org Lett, 7:1561-4, 2005
Moore JC, et al., Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. Cancer Lett, 98:83-7, 1995
Paik IH, et al., Second generation, orally active, antimalaria, artemisinin-dereved troxane dimmers with high stability, efficacy and anticancer activity. J. Med. Chem, 49:2731-4, 2006
Posner GH, Ploypradith P, Parker MH, et al: Antimalarial, antiproliferative, and antitumor activities of artemisinin-derived, chemically robust, trioxane dimers. J Med Chem 42:4275-4280, 1999.
Posner GH, et al., Anti-cancer and anti-malaria efficacy and safety of artemisinin-derived trioxane dimmers in rodents. J. Med Chem. 47:1299-301, 2004
Rowen R, Artemisinin: From Malaria to Cancer Treatment, Townsend Letter for Doctors & Patients, December 2002
Sadava D, et al., Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. Cancer Lett. 179:151-6, 2002
Schaller J., Artemisinin, Artesunate, Artemisinic Acid and Other Cerivatives of Artemisia Used for Malaria, Babesia and Cancer, Hope Academic Press, Tampa, Florida, 2006, p.55
Singh NP, Lai H: Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci 70:49-56, 2001
Singh NP, et al., Artemisinin induces apoptosis in human cancer cells. Anticancer Res. 24: 2277-80, 2004
Singh NP, et al., Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells. Anticancer Res. 25:4325-31, 2005
Sun WC, Han JX, Yang WY, et al: [Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro]. Zhongguo Yao Li Xue Bao 13:541-543, 1992.
Yamachika E, et al., Artemisinin: an alternative treatment for oral squmous cell carcinoma. Anticancer Res. 24:2153-60, 2004
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