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Artesunate Edited 030708

Artesunate Edited 030708

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[The Sino Med Research Institute does not advocate the use of artemisinin and its derivatives to treat

disease. Although it is recommended by the World Health Organization as a treatment for malaria, the U.S. Food and Drug Administration (FDA) does not currently approve the use of artemisinin and its derivatives for the treatment of any disease. Research on artemisinin and its derivatives and cancer is still in the very early stage. Human use of them should be considered experimental and taking artemisinin or its derivatives and any supplements should be approached with caution. If you are seeking treatment for any medical disease, please consult a qualified health care professional.]

Artemisinin, Its Derivatives and Cancer Qingcai Zhang Sino-Med Research Institute New York 1. From Malaria to Babesia to Cancer Artemisinin is an active ingredient extracted from the traditional Chinese medicinal herb Qing Hao (Herba Artemisiae annuae), a sweet wormwood plant. In more than three decades, Artemisinin and its molecule-modified derivatives, such as artesunate, have undergone extensive basic and clinical studies for its anti-malaria effects. As a result, the World Health Organization has stated artesunate as the first line treatment for malaria. Since then, millions of malaria patients have been successfully treated with artesunate and it was also shown to be effective in cases of drug-resistant malaria. Articles are available documenting the extensive pre-clinical and clinical studies that have been done. (Bharel S, et al., 1996, Gulati A et al., 1996) Babesia is a malaria-like protozoa infection of the red blood cells and a common co-infection of Lyme disease. In Zhang Clinic, we have found artesunate to be an effective treatment for Babesiosis as well. Current research on artesunate is starting to reveal its potentials in cancer treatment. (Efferth T, et al., 2001) Currently, Zhang Clinic is using artesunate as a non-toxic adjunctive treatment for supporting the health of cancer patients.

2. Pre-Clinical Studies— Anti-Malaria, -Babesia, and -Cancer Mechanisms The mechanism of anti-malaria and babesia protozoa action of artemisinin and its derivatives is speculated to be related to the iron metabolism of protozoa. Its molecular peroxide group produces reactive oxygen atoms, which can interfere with the iron metabolism of protozoa. Iron is required for cell division as cancer cells can aggressively accumulate iron for their rapid cell reproduction. Artemisinin and its derivatives can interfere with this type of abnormal cell reproduction and promote the cell to enter apoptosis (Schaller J, 2006). Artemisinin and its derivatives have been shown to affect 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 invade and grow in erythrocytes (red blood cells), have the opportunity to accumulate 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. Knowing

df=1. iron is released and can readily react with the artemisinin tagged to the transferrin.. The cells were then pelleted and transferred to a culture media containing 200 microM of a derivative of artemisinnin. df=l. the existence of heavy iron load seems to be a condition required for artemisinin and its derivatives to suppress cancer cells. 2001) Similar anti-cancer activities have also been found in other derivatives of artemisinin. et al. (Efferth T. No necrotic cells were observed. Lee CH. Once inside the cell. 2004).. 2006. normal cell cultures without heavy iron loads were not affected. This in turn. 2002) The following cancers were shown to have the highest sensitivity to these substances: leukemia. both iron and artemisinin would be transported into cancer cells in one package. Thus. When these iron-loaded cells were treated with artemisinin. et al. (Singh NP. 75% died within eight hours and nearly 100% died within 24 hours. 2000. It was found that DHA treatment significantly decreased cell counts and increased the proportion of apoptosis in cancer cells compared to the controls (chi2=4. The addition of holotransferrin further decreased cell counts significantly (chi2=4.. This has been confirmed in animal studies. et al. they published a paper in Cancer Letters regarding the use of artemisinin against numerous cancer cell lines in vitro. In the control. et al. df=l.. such as arteether. One of the derivatives of artemisinin.. prostate cancer.035). Increasing the amount of iron in cancer cells could enhance this effect.. 2001). dihydroartemisinin (DHA) and then incubated. researchers Henry Lai and Narenda Singh of the University of Washington became interested in the possible positive effects artemisinin may have against malignant cells. Paik IH. 2006.. 2006. 2001. Lai and Singh found that after tagging artemisinin to transferrin. et al.that there is a high accumulation of iron in cancer cells. et al. artemether and dehydroartemisinin (Singh NP. 1995) and it is believed that the main cancer suppressing mechanism of artemisinin and its derivatives is in the peroxide-oxygen spark that occurs inside the . It was found that the holotransferrin-tagged artemisinin was both potent and selective in killing cancer cells. et al.. Singh NP et al. Galal AM.035) and increased apoptosis (chi2=4.. They further confirmed this theory and reported that artemisinin-tagged holotransferrin can enhance the selective cancer cell killing effects of artemisinin and were not toxic to normal cells.. In 1995. enhanced the selectivity of artemisinin’s effects on cancer cells. Singh NP. et al.5. and melanoma. 2002) It has also shown suppressive effects on following cancers: breast cancer. Anfosso L. (Moore JC. and did not cause harm to normal cells. it was concluded that the 'tagged-compound' could potentially be developed into an effective chemotherapeutic agent for cancer treatment (Lai H et al. has been tested to have the effects to suppress 14 different types of human cancer cell lines. Cell cultures of drug-resistant breast cancer were found to have a high propensity of iron accumulation. Efferth T. It was 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.. 2005. brain cancer. et al. (Berger TG et al.. et al. et al. (Galal AM. Lai H.. 2002. deoxyartemisitene.035). 1995) Thus. (Lai H et al.. reported that cancer cell lined Molt-4 cells were first incubated with 12 microM of human holotransferrin to enhance the iron supply to the cells. ovarian cancer..5. p<0.. 2005). Another anti-cancer effect of artemisinin and its derivatives is the ability to promote cancer cells to enter apoptosis (programmed cell-death).5. et al. colon cancer. This was then tested on a human leukemia cell line (Molt-4) and normal human lymphocytes. kidney cancer and others. This article has mobilized interest in artemisinin as an addition to cancer treatment. p<0. 1995). p<0.

Intermediate GI50 values were obtained for melanomas.. the oxidant vulnerability is dramatically enhanced due to unbound iron during cell division. immune support.13 microM respectively. Artesunate was shown to be most active against leukemia and colon cancer cell lines. Leukemia lines resistant to doxorubicin. The Dr.1985). can be enhanced. et al. both of which degrade hydrogen peroxide. since all of these protective antioxidant enzymes are often deficient in transformed cancer cells. especially associated with the mitosis phase of cancer cells. methotrexate. prostate. none of these drug resistant lines showed resistance to artesunate. The higher iron fluxes. USA. Clinical Observations Clinically. Dr. and spiritual work. 2002). Most importantly. He emphasizes that it should be used in a professional medical settings together with complementary strategies employing detoxification.cancer cell. 2002).62 microM) indicating the lowest sensitivity towards artesunate. The theorized reason for this is the absence of a tertiary amine in artesunate (required for cellular transport systems to usher the drug outside the cell). He believes that artemisinin will prove to be one of the most powerful therapeutic agents in cancer treatment. The manganese in mitochondria and copper zinc in cell cytoplasm are generally lower in cancer cells. and with no observed toxicity (Rowen R.. ovarian. (Efferth et al. (Singh NP. Efferth T.. Cancer cells are deficient in antioxidant enzyme superoxide dismutase. especially dihydroartemisinin. et al. Non-small cell lung cancer cell lines showed the highest mean (GI50 26. breast. the profound catalase deficiency in cancer cells is credited with creating vulnerability to oxidants. a comparison of artesunate’s cytotoxicity with currently used cytostatic drugs showed that artesunate was active in micro molar ranges comparable to those of established anti-tumor drugs. NP Singh has been following a series of cancer patients with nearly universal improvement while being treated by artemisinin or its derivatives. diet. It is the deficiencies in antioxidant enzymes lead to the use of many types of common chemotherapeutics that are superoxide generators. 3. or hydroxyurea were tested. Normally. The mean 50% growth inhibition (GI50) concentrations for them were 1.. . 2000) These effects work together to promote cancers cell entering apoptosis. 2006) The current theory is that if we can increase cellular iron load by using a method such as holotransferrin then the efficacy of cancer treatment by these derivatives. Remarkably. should render these cells more susceptible to oxidative damage via hydrogen peroxide and superoxides. Cancer cells are also grossly deficient in catalase and glutathione peroxidase. CNS. vincristine. 2001) Another possible mechanism is that these substances can combine with and alter the functions of certain proteins unique to cancer cells. (Schaller J.. Hoang has observed a 50-60% longterm remission in over 400 cancer patients utilizing artemisinin together with a comprehensive cancer strategy. and renal cancer cell lines. et al. This is one of the anti-cancer mechanisms of artemisinin and its derivatives (Levine SA. (Lee CH. et al. (Singh NP. 2001) Artesunate demonstrated dramatic cytotoxic activities against a wide variety of cancers including drug resistant cell lines. However. and has been analyzed for its anti-cancer abilities against 55 types of cancer cell lines by the Developmental Therapeutics Program of the National Cancer Institute. (Rowen R. Artesunate is a semi-synthetic derivative of artemisinin. et al. which is present in virtually all currently used chemotherapy drug agents..11microM and 2. 2006. 2004).

Fran also had type II diabetes. Combining with other traditional Chinese medicine (TCM) herbal formulas were used as supportive agents to improve the patient’s survival and life quality. 8. lesions have been treated by surgery or trans arterial chemoembolism (TACE) and alcohol or radiofrequency ablation. She had severe fatigue and insomnia. or radiotherapy. Three cases of biopsy-confirmed stomach intestinal epithelium metaplasia. have a wide anti-cancer spectrum. anemia. the other in segment 6. and oral cancers. the artesunate treatment was able to stabilize and shrink the smaller lesions. every patient had untreated HCC lesions in their liver. We use artesunate (active ingredient of Artemisia Capsule) as the main treatment agent. which was slightly exophytic. mild ascites and edema. 2000. Hepatocellular Carcinoma (Liver Cancer): Our clinic has been treating many patients with viral hepatitis B and C. leukopenia (WBC 2. we also focus treatment on restoring liver function and controlling liver inflammation.7 x 3. In addition to the liver conditions. The treatments consisted of embolism on both lesions and alcohol ablation on the lower lesion. such as artesunate. A physical check also showed an enlarged spleen consistent with portal vein hypertension. chemotherapy. From our clinic experience.In Zhang Clinic.9 x 3. breast cancer. She had been diagnosed with hepatocellular carcinoma (HCC) and hepatitis C in the de-compensated cirrhosis stage. The following are two patient case studies: Case 1 Fran was 73 when she first visited Zhang Clinic on Dec. 14. In several patients diagnosed with cervical dysplasia by PAP smear. Patients in the advanced stages are at risk for developing HCC. As her treatment options were limited. Subsequent GI biopsies found that the metaplasia was no longer there. In patients with cancer diagnoses or those already finished with conventional oncology treatments. The higher lesion was not treated with ablation due to its location being too close to the lung.3). multimylenoma. and bile retention. For those patients who had main cancer lesions removed by surgery. In every case.3 mg per capsule) three times a day for two months. we have been using artesunate for treating pre-cancerous conditions. liver inflammation.0 cm. two lesions were found on her liver: one high in segment 8 measuring 2.Kettering Institute. follow-up PAP smear checks for dysplasia turned to negative. which is a pre-cancerous condition of stomach cancer.8). every HCC patients showed longer than expected survival time while overall life quality was improved. When they initially came for treatment. lymphoma. Artemisia Capsule was used as adjunctive supporting treatment. they have been clinically tested for treating following various common cancers. After artesunate treatment. elevated ammonia (69. low platelets (60). 2000.4 cm. treated with Artemisia Capsule (contains artesunate 33. We have seen promising results in treating hepatocellular carcinoma (HCC). most of these lesions became stabilized and some scattered smaller lesions disappeared. she came to Zhang Clinic seeking alternative methods. In those patients whose major cancer lesions were treated by oncologic therapies but still had untreated lesions. Symptoms included light jaundice. In addition. In some of these patients. Allicin Capsule and Artemesia Capsule (both used as vaginal suppository) was used for several weeks. She was also physically too weak at that time to tolerate ablation treatment for both lesions. Fran was treated at the Sloan . and measured 3. Our treatment goals focused on restoring her liver functions and . Following an MRI performed on Nov. urine bladder cancer. artesunate treatment was used as a preventive measure for possible relapse and metastasis. Since artemisinin and its derivatives. gallstones.

It was found that the lesion at segment 2 was further reduced in size to 1. on April 29 2005. 2005. we started herbal treatment with formula R-6532 Capsule. Since her cancer load was significantly reduced by surgery and radiofrequency ablation. 18. The Cordyceps Capsule was also used to improve cellular immunity and Circulation P formula used to improve blood rheology and microcirculation. a modified version of TCM formula Kang Ai Bao (Wang HZ et al. The lesion in segment 2 has decreased in size from 2.9 x 3. and the ammonia levels normalized. Following the surgery no chemotherapy or radiotherapy was used.7 x 3. (Liu Y. The small lesions in segment 8 were not treated. (from 3. 2004. AFP decreased from 12 to 3. a large tumor (8. new lesions were discovered in segment 7 and 6. All lesions were found in the right lobe of the liver. After 3 months on treatment. another MRI was performed and compared with the MRI done on 10/4/04 and 4/5/04.0 cm) and the lower lesion had decreased in size to 2. #2 Capsule. A hypervasular lesion in hepatic segment 8 is stable.3 cm. This was her status when she first visited Zhang’s Clinic. studied to combine artemisinin and its derivatives with large carbon molecule. she underwent liver resection surgery. Since then. At the time of her diagnosis.2 and previous hyper intense foci scattered throughout the liver were no longer seen. ALT and GGT levels were normal but AST was mildly elevated. a few smaller lesions were found in segment 8.controlling the cancer. 2001 revealed that the size of the higher lesion had decreased to 1.2x1. The lesion in segment 2 was treated by radiofrequency ablation. Fran is now 81 and enjoys a good life quality despite her compromised liver functions 8 years after the HCC diagnosis. At this point we added Artemisia Capsule. The R-6532 Capsule. After 10 months on this protocol. the HCC cell killing effects of these artemisinin derivatives was showed to be 200 times more effective. One year later. a liver protective formula. The large tumor in segment 5 and 6 was removed by liver resection. which can dramatically enhance its antiHCC effects. jaundice cleared.1 cm (from 2. She has since had a yearly MRI check-up and the liver lesions remained stable. By using large carbon chains. an MRI was conducted to compare with the one done prior to the herbal protocol on 9/17/03. Sun WC. The findings of this comparison read: The patient is status post resection of hepatic segments 5 and 6. Other previously noted smaller lesions in right hepatic lobe are no longer seen. et al.6 cm) was found in segment 2.4x1. Case 2: Margaret was 58 she first visited Zhang Clinic. 2003.4 while AST was still slightly above normal range. Thereafter. et al. Fran’s general health and liver functions were strong enough to tolerate embolism and alcohol ablation treatments and were successfully completed. et al. Hepa F.4 cm). At the same time.. On April 5. 1992) . approximately one year after her surgery and seven months into herbal treatment.6 cm to 1.6 cm.1 x 1. such as aslipophilic alkyl carbon chains. and Sun WC.7 x 2.5 cm) was found in segment 5 and 6 and one (2. Fran’s liver functions had improved. 1997) was used along with a liver supportive protocol. most liver functions were in normal range. et al. Margaret’s liver function tests were all within normal range. a CAT scan was done every 6 months. cholecystectomy and radiofrequency ablation of a lesion in segment 2.. the main constituent being artesunate.2 x 1.8x1. Liu Y. No new lesions were found. Her lesions are checked every 6 months and have been stable. In addition. No new lesions were detected. Blood tests showed her AFP was elevated (12) after surgery. we have added artesunate (Artemisia Capsule) in her protocol to treat residual cancer cells and help prevent possible relapse. On Dec. A CAT scan performed on July 19. She had been diagnosed with HCC in May of 2003. Four months prior to her visit at Zhang Clinic. ascites and edema eliminated. At this time. was used to help restore her liver functions.

she received a series of IPT (insulin potentiation therapy-low dose chemotherapy). is a woman in her 40s diagnosed with breast cancer. artesunate and allitridii (the active ingredient of Allicin Capsule) mixtures have been used as a vaginal suppository to treat cervical dysplasia diagnosed by PAP smear. In Zhang Clinic. and detoxification strategies. and dendritic cell vaccine. she began treatment with artemisinin and a variety of complementary strategies.. Upon further testing. (Lai H.. reported that when used topically in animal studies. including diet.. artemisinin and it derivatives. vertebral collapse and local neurological impairment.L. a 47 year-old Alaska resident with stage IV breast cancer developed metastasis into vertebral T1 with significant pain. supplements. plus oral artemisinin 300 mg twice a day. it was found that applying dihyroartemisinin (DHA) in the cervical regions of dogs that were then exposed to HPV DHA strongly inhibited HPV induced cancer development (Disbrow GL. The degree of pain immediately decreased and her comment after two weeks on artemisinin was: "Last week I thought I was dying. Cervical Cancer: Since cervical cancer cells have large numbers of transferrin receptor to increase iron uptake. diet and detoxification strategies.” (Rowen R. which has been continued..” (Rowen R. et al. Her physician believes the regressed mass has now turned to scar tissue. Six months later she reported that she no longer experienced symptoms and her quality of life was dramatically improved. et al." Four months into therapy using oral supplements. The cancer-induced rats were fed food containing 0.E. chemically induced breast cancer could be prevented and treated by Artemisinin. and today for the first time in months. scans did not confirm definite cancer activity anywhere else.. 2005). high dose vitamin C infusions. Most symptoms had cleared within 4 months (October 2001). Disbrow GL. A case history reported by Townsend Letter for Doctors & Patients reads: “Patient D. she received artesunate intravenously (source: China). et al. 2002). 2002). (Singh NP. whereas 96% of the rats in control group without artemisinin treatment developed cancer. et al. found that in rats.Breast Cancer: Lai H.02% of artemisinin for 40 weeks and found that only 43% of the rats actually developed cancer. This method has been used for several years and our clinical observations showed that not one patient relapsed or developed metastasis so far. Thereafter. In addition. First seen May 2001. 2001) In Zhang Clinic. I believe I am going to live. dietary management. treated human breast cancer cells with holotransferrin and dehydroaremisinin together and found that this combination was able to kill a type of radiation-resistant human breast cancer cells and showed no harmful effects on normal human breast cells. 2006) Singh NP. such as artesunate and dihyroartemisinin (DHA) showed strong suppressive effects against cervical cancer cells and did not show harmful effects on normal cervical tissue. Even in cases of widely metastatic breast cancer. chemotherapy and/or radiation treatments. Another case report reads: “L. she experienced very painful bone metastasis cover most of the spine. detoxification and Kelly type proteolytic enzymes. et al. et al. these substances combined with other alternative supplements showed good results. Follow up PAP smear results of all . artesunate was used for breast cancer patients to help prevent relapse and metastasis after surgery. even in places where cancer was previously found. In January 2002. She had received limited radiation therapy to reduce the pain in the thoracic spine. a positron emission computerized tomographic (PET) scan showed no cancer activity in her spine.

2006) Other Cancers: Other types of cancer have also been studied by using artemisinin and its derivatives. The skin cancer lesion was eliminated within a few days. When tested separately.A. Leukemia and Lymphoma: Singh NP et al. et al. (Singh NP.5 cm. Topical artemisinin (artemisinin in 50% DMSO) applied twice daily caused the large lesion to disappear after 5 days and the other smaller lesions appeared to be decreasing.. This treatment has been able to help keep blood counts within the normal range. it was also found that when antioxidants were used.. the glioma cells become more sensitive to radiation treatment. 2005) In Zhang Clinic artesunate has been used as adjunctive support treatment for patients with chronic lymphocyte leukemia (CLL). respectively. At the end of two weeks.” (Rowen R. a depression appeared at the apex of the tumor.” (Rowen R. the life expectancy of this type of cancer is less than a few months (Berger TG. et al. during DHA treatment. These include . The patient had metastatic melanoma and failed to respond to chemotherapy. skull surface smooth. a 47 year-old mechanic who was presented with a 4. These two substances seemed to exhibit synergetic effects. reported on their observation in treating metastatic melanoma with artemisinin. reported that when artemisinin and sodium butyrate were used together. and tremendous inflammatory erythema. Artesunate. The case report reads: “Patient F. free radical scavengers or antioxidants should not be used. the mass was completely gone. found that when dihyroartemisinin (DHA) was used together with the radiation. 2002) Glioma: The brain tumors usually not sensitive to chemotherapy so conventional treatment is mainly radiation therapy. Generally speaking. When tested as a combined treatment. After using artemisinin. an 81 year-old Californian with multiple skin cancers including one active recurrent quarter-sized lesion that had been burned 4 times previously. Four weeks later. This combination did not harm normal white blood cells and lymphocytes. the patient is still alive four years after advanced melanoma was diagnosed. They also found that when the glioma cell culture was treated with DHA. 100% of the leukemia cells were killed within one day. (60mg) was injected muscularly 14 consecutive days and while the patient changed his diets to high proteins/vegetables (Kelley parasympathetic type diet). Non-Hodgkin’s lymphoma on the right side of his head. the combination dramatically enhanced artemisinin’s suppressive effects on leukemia cells. In skin cancer. (Kim SJ. artemisinin and butyrate showed suppression rates on leukemia cells of 40% and 32%. Kim SJ et al. Another case reported the use of artesunate DMSO solution applied topically. the reduction of the colonies was more obvious.A... the number of cell colonies was reduced and when radiation was given together with DHA treatment. artemisinin and its derivatives can be used as a topical application. the cancer was at first stabilized and then the metastatic lesions in the lung and spleen were later found regressed. When the report was writing. the effects of DHA was blocked. 2002) Melanoma and skin cancer: Berger TG.patients turned to normal within a few weeks of treatment. et al. A case history from the Townsend Letter for Doctors & Patients reported: “Patient D. with gaping incision from a recent biopsy. In their study. Therefore. et al. He was tested to be free of cancer 6 months later.. 2005). incision totally healed and erythema virtually cleared.

ovarian cancer (Chen HH. Its non-cytotoxic anti-cancer mechanism could possibly open a brand new field of anti-cancer research   and made the development of non-toxic gentle and humane anti-cancer treatment possible. 2003). et al. the most common co-infection of Lyme disease.. reported that artemisinin derivatives had strong suppressive effects on prostate cancer. et al. fibrosarcoma (Moore JC. now showed a non-small cell lung carcinoma in the right lower lobe. 4. After 4 months. Summary For more than three decades. Posner GH et al. the tumor shrunk to 1x2 cm and her oncologist felt this actually represented scar tissue and declared her cancer free.stomach cancer (Sun WC. 1999. Artesunate in the treatment of metastatic uveal melanoma – first experiences. Oncol Rep.. healthy most of her life. On the cost basis it was much less expensive than most chemotherapy drugs. et al.. astrocytoma (Efferth T. et al. et al. we at Zhang Clinic have been using it for treating babesiosis. prostate cancer. chemotherapy.. et al. 2004). or radiation treatments to help prevent relapse and metastasis. It has showed to be able to selectively affect cancer cells without harming normal cells. . et al. 2005. Its molecularly modified derivative artesunate had been recommended as the first-line anti-malaria treatment by the World Health Organization. its efficacy has proven to be greater than conventional medications in treating babesiosis. an 83 year old Toronto resident.M. et al.2004). 2006 Berger TG. 2004). ” Her heart condition also improved considerably with CoQ10. 600mg daily (Rowen R. The patient received artemisinin 500mg twice a day and Carnivora oral. Because of the similarities between babesiosis and malaria. A case reported on NSCLC in Townsend Letter for Doctors & Patients reads: “Patient V. Artemisinin and its derivatives have been used for treating malaria and millions of patients have been successfully treated. Because it is non-toxic and it has very wide anti-cancer spectrum. et al.. 1995). considered non-resectable due to the risk of heart failure and circulatory problems. 2002). et al. and non-small cell lung cancer (NSCLC)… etc.. References: Anfosso L. Kaposi’s sarconma (Dell’Eva R. 2002). Because the anti-malaria and anti-babesia mechanism of artemisinin and its derivatives is shared by cancer cell division since 1995 researchers at the University of Washington started its anti-cancer studies.. 14:1599-603 . Microarray expression profiles of angionenesis-related genes predict tumor cell response to artemisinins. Pre-clinical and clinical studies found artemisinin and its derivatives to be potent anti-cancer substances with no obvious toxicity to normal cells in therapeutic dosages. (Posner GH.. 1992). It can also be used after surgery.. From our experience. Artesunate is more potent and showed less side effects compared to artemisinin.. oral squamous cell carcinoma (Yamachika E.. via nebulizer 5cc twice a day. 2004). 6:269-78.. it can be used immediately after cancer diagnosis to prepare the patient for additional oncotherapies. which seems to be an ideal anti-cancer treatment. Pharmacogenomics J. small-cell lung cancer (Sadava D.

l996. et al. Efferth T. et al. Efferth T.. Biochem Pharmacol 64:617-623.: NMR studies on novel antitumor drug candidates.. 2000. Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro.. Experimental Studies on Artemisia. Srivastava M. Bharel S. Bauer R: mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate. et al. Gulati M. Dell’Eva R. et al. Shin J. 1996. 2006 Lee CH. Sauerbrey A. 65:10854-61. 2006 Lai H.. 231:43-8. Structure biosynthesis and functions of artemisinin. Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Srivastava S. Oral artemisinin prevents and delays the development of 7.. 65:184-8. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. Int J Oncol 18:767-773. 1995. Fitoterapia Vol LXV11 No 5. Deoxyartemisinin derivatives from photooxygenation of anhydrodeoxydihydroartemisinin and their cytotoxic evaluation. Lai. Cancer Latt. Fitoterapia Vol LXVII No 5.Bharel S. J. Bio-chem Pharmocol. et al. 7:407-21. Biochem Biophys Res Comm 274:359-369. H. et al. Kim SJ. 76) (No. .12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in the rat. Life Sciences. 2002. Molecular pharmacology and pharmcogenomics of artemisinin and its derivatives in cancer cells. 2005 (Vol. et al. Cancer Res. Nat Prod. arteether. 2006 Galal AM. 2002 Gulati A.. 68:2359-66. Abdin P. 2001. Inhibition of angiogenesis in vivo and growth of Kaposi’s sarcoma xenograft tumors by the anti-malaria artesunate.. Hong H. et al. 11) 1267-1279 Lai H." Pharmacol Res 48: 231-236. et al. 37:998-1009. Dihyroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo. and artemether. deoxoartemisinin and carboxypropyldeoxoartemisinin. Singh NP: Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin.. 2003. Olbrich A. Curr Drug Targets. Free Radic Bio Med. Abdin MZ. an herbal remedy for malaria. Cancer Res Clin Oncol. Dunstan H. Effects of artemisinin-tagged holotransferrin on cancer cells.. et al.. Cancer Lett 91:41-46. 132:1`29-35. 2004 Efferth T. 2005 Efferth T. J. 2004 Disbrow GL. et al: The anti-malarial artesunate is also active against cancer. Chen HH..

7:1561-4. Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. 1995 Paik IH. et al. Med. Cancer Lett. CJITWM. antiproliferative.. 2004 . Artemisinic Acid and Other Derivatives of Artemisia Used for Malaria. Artemisinin induces apoptosis in human cancer cells. and antitumor activities of artemisinin-derived. Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells. Tampa. 47:1299-301. efficacy and anticancer activity. 1985.. Han JX. 98:83-7. 2002 Schaller J. Anti-cancer and anti-malaria efficacy and safety of artemisinin-derived trioxane dimmers in rodents. 1992. Zhongguo Yao Li Xue Bao 13:541-543. Anticancer Res.. Second generation. trioxane dimers. Artemisinin. Chem. 2006. Posner GH. 17(12):730-732 Yamachika E.Levine SA. California. et al. Yang WY. orally active. Antioxidant Adaptation: Its Role in Free Radical Pathology. 1997.. Synthesis and cytotoxicity studies of artemisinin derivatives containing lipophilic alkyl carbon chains.. et al. 2001 Singh NP... et al.. 25:4325-31. artemisinin-dereved troxane dimmers with high stability. December 2002 Sadava D. 24: 2277-80. Parker MH. Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. et al. Artemisinin: an alternative treatment for oral squmous cell carcinoma. 2004 Rowen R. Allergy Research Group. Hope Academic Press. 49:2731-4. Babesia and Cancer.55 Singh NP. 24:2153-60. Cancer Lett. 1999. Clinical Study on Effect of Kang Ai Bao Oral Liquid in Treating 103 Malignant Tumor Patients. et al. J. Org Lett. Ploypradith P. Artemisinin: From Malaria to Cancer Treatment. Wang HZ et al. Life Sci 70:49-56. Med Chem. antimalaria. et al: [Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro]. Florida. J. Lai H: Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. et al: Antimalarial. 2006 Posner GH. 2004 Singh NP. 2005 Moore JC. 179:151-6.. 2005 Sun WC. et al. San Leandro. Anticancer Res. Kidd PM. Anticancer Res. et al. p. Townsend Letter for Doctors & Patients. Artesunate. chemically robust. J Med Chem 42:4275-4280. Liu Y.

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