TERAPIA ANTICANCER CON ARTEMISININA
La Artemisia Anua (Qing Hao, en chino) es una planta usada en Medicina Tradicional China para combatir la malaria, parásitos intestinales, enfermedades febriles, y tumores malignos. La Artemisinina es el ingrediente activo de la Artemisia Anua y es la medicina más efectiva hasta ahora conocida contra la malaria. Estudios también demuestran que la Artemisinina posee poderosa acción citotóxica selectiva contra las células malignas y poco, casi ningún efecto secundario cuando se usa apropiadamente.
La artemisinina es un endoperoxida (agente con fuerte acción oxidativa) que se activa en contacto con el hierro y tiene una gran afinidad por el hierro intracelular (las células de cáncer presentan más receptores de hierro y mayor contenido de hierro intracelular que las células normales); precisamente mediante ese mecanismo es que la Artemisinina se aloja selectivamente en las células cancerosas y las destruye mediante reacción oxidativa fulminante.
La Artemisinina comúnmente se administra vía oral, intramuscular o endovenosa. La Artemisinina se absorbe pobremente en el tracto digestivo, pero en pequeña dosis es todavía efectiva contra la malaria. Sin embargo, la Artemisinina para terapia oncológica requiere una dosis mucho mayor que la dosis que comúnmente se administra a pacientes con malaria.
La dosificación de la Artemisinina oncológica se realiza de acuerdo al peso corporal del paciente y la administración es por inyección intramuscular, inyección intraperitoneal, inyección intratumoral, o infusión endovenosa. Los protocolos de tratamiento con Artemisinina para terapia oncológica además, requieren monitoreo con análisis de laboratorio y supervisión clínica profesional. Típicamente, la Artemisinina para aplicación antineoplásica se administra en un centro de salud.
El Dr. Marcelo Lam es uno de los médicos con más conocimiento y experiencia en la aplicación de la Artemisinina contra el cáncer. Prestigiosos oncólogos a nivel mundial han adoptado los protocolos de tratamiento del Dr. Marcelo Lam, para el uso oncológico de la Artemisinina.
La Artemisinina oncológica se puede usar sola o de forma complementaria en combinación con tratamientos convencionales. En China, la Artemisinina está disponible en combinación con Gendicine y Oncorine (H101) (terapia génica antitumoral), crío-ablación, HIFU, hipertermia, y otros procedimientos.
Esta terapia está disponible en nuestra clínica en Miami. Nuestra alianza médica internacional además, facilita el acceso a esta terapia en Centros de Salud de primera línea en China y en la República Dominicana. Contacto
Veaamos los siguientes reportes publicados en ingles sobre las investigaciones científicas de la Artemisinina contra el cáncer:
Al final de esta pagina también hay una lista de "enlaces" que dirigen a otras publicaciones sobre la Artemisinina y su uso en la lucha contra el cáncer.
Lista de Referencia:
CELL OF A HUMAN LEUKEMIA CELL LINE
In another study, researcher Dr Lai noted even more amazing results involving leukemia cells. He mentioned that the cancer cells were destroyed very quickly within a few hours when exposed to holotransferrin (which binds with transferring receptors to transport iron into cells) and dihydroartemisinin (a more water-soluble form of artemisinin). He further explained that it might be because of the high concentration of iron in the leukemia cells. (H.Lai and NP Singh, Selective Cancer Cell Cytoxicity from Exposure in Dihydroartemisinin and Holotransferrin, Cancer Letters, 91:41-46, 1995)
55 CANCER CELL LINES
This amazing herb was also examined for its activity against 55 cancer cell lines. It was found to be the most active against leukemia and colon cancer and active against melanomas, breast cancer, prostate cancer, CNS and renal cancer. It was also reported that artemisinin's effectiveness was comparable with other standard drugs used to combat cancer. As such, these results and the low toxicity of artemisinin had made this herb to be a potential for cancer chemotherapy. (Efferth et al, Anti-Malaria Drug is Also active against cancer, Int'l Journal of Oncology, 18;767-773,2001.)
BREAST CANCER CELLS
This herb becomes cytotoxic in the presence of ferrous iron. To accommodate a rate of iron intake greater than normal cells, cancer cells surfaces feature greater concentrations of transferrin receptors- cellular pathways that allow iron into a cell. In breast cancer cells, they have 5 to 15 times more transferrin receptors on their surface than normal breast cells. During a recent study, both breast cancer cells as well as normal cells were injected with artemisinin. The results showed that artemisinin effectively killed radiation-resistant breast cancer cells in vitro. However, the effects on the normal breast cells were minimal. This simply goes to show that this herb might be a simple, effective and economical treatment for cancer. (NP Singh and H Lai, Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sciences, 70:49-56,2001)
SMALL-CELL LUNG CARCINOMA CELLS (SCLC)
When artemisinin was tested on drug sensitive (H69) and multi-drug resistant (H69VP) SCLC cells which were actually injected with transferrin to raise the iron concentration levels, it was found that the cytotoxicity of artemisinin for H69VP cells was ten times lower than for H69 cells. This concluded that artemisinin was part of the drug resistance phenotype. This experiment also indicated that pretreatment of H69 did not lower the iron concentration for artemisinin whereas for H69 VP cells, the iron concentration was lowered to near drug sensitive levels. The researchers therefore concluded that artemisinin could be used together with transferin in drug resistance SCLC. (Sadava, D et al, Transferrin overcomes drug resistance to artemisinin in human small cell lung carcinoma cells, Cancer Letter, 179,151-156, 2002)
ENHANCED EFFECTIVENESS OF CHEMOTHERAPY
Various studies carried out separately in Germany and Australia, revealed the activities of twenty drugs on leukemia CCRF-CEM cells lines, artemisinin, artesuante, balcalein, baicalin, barberine, bufalin, cantharidin, cephalotaxine, curcumin, daidzein, daidzin, diallyl, disulfide, ginsenoside, Rh2, glycirrhizic acid, isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin, quercetin, tannic acid and tetrahydronardosinon. The results showed that artesunate increased daunorabicin accumulation in CEM/E1000 cells. As artesunate and bufalin both have abilities to combat leukemia, whether it was applied alone or together with daunonrubicin in multi-resistant cells, these two drugs might be suitable for treating leukemia in the near future. (Efferth et al, Blood Cells, Molecules, and Diseases 28(2) Mar/April; 160-168, 2002)
MODULATION OF MULTIDRUG RESISTANCE FOR CHEMOTHERAPY
Arteminisin could prevent the spread of cancer cells and increase cytotoxicity of perarubicin and doxorubicin in P-glycoprotein-overexpressing, and in MRP- overexpressing, but not in their corresponding drug sensitive cell lines. (Reungpatthanaphong, P et al Modulation of MDR by Artemisinin, artesunate and DHA in K562, GLC4 Resistant cell lines, Biology Pharmocology Bull. 25(12) 1555-1561, 2002)
5 CANCER CELL LINES
When a triterpene and a sesquiterpene were isolated from separation of artemisia stolonifera, both of them proved to be able to destroy cancer cells in non-small cell lung adenocarcinorma, ovarian cancer, skin melanoma, CNS and colon cancer. (Kwon, Phytochemical constituents of Artemisia stolonifera, Arch.Pharm, Research 24(4):312-315,2001)
LEUKEMIA AND NON SMALL-CELL LUNG CARCINOMA CELL LINES
Researchers discovered a novel class of compounds that could destroy cancer cells after modifying artemisinin in one of the experiments conducted recently. This new derivative contained cyano and aryl groups and was very effective in destroying leukemia and human lung carcinoma cells. (Li, Ying, et al, Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle, Bioorganic and Medicinal chemistry letters 11:5-8, 2001)
Some artemisinin related endoperoxides that were tested on their abilities to destroy Ehrlich ascites tumor cells (EAT) were proven positive. Surprisingly, its derivatives were even more powerful at destroying cancer cells. This test also confirmed artemisinin and its derivaties abilities to kill EAT cells at higher concentration than those needed for in vitro anti-malaria activities. (Woerdenbag, HJ et al. Cytotoxicity of artemisinin-related endoperoxides to EATcells, J Natural Products 56(6), 849-856, 1993)
BLOOD-BRAIN BARRIER & ALZELMER'S DISEASE (AD)
Although artemisinin could not be dissolved in water, it was able to cross the blood brain barrier. It might therefore be useful for curing brain tumors and other brain diseases.
During a recent experiment, an alkaloid of artemisia asiatica was metabolized to small molecules in the digestive tract and was passed through the blood brain barrier. The results showed that it could act as an acetylcholinesterase inhibitor with a blocker of neuroloxicity induced by a beta in human beings that caused AD. (Heo et al, Inhibitory effects of Artemesia alkaloids on acetylcholine sterase activity from PC12 cells, molecule cells, Jun 30:10(3):253-262)
Clinical Trials Using Artemisinin:
HUMAN LARYNX CANCER TREATMENT
In this case, the patient was given artesunate injections and tablets over a period of nine months. His tumor was significantly reduced by about 70 percent just after two months of treatment. The patient also reported that he benefited much from this treatment. It actually prolonged his life and improved his quality of life. Once again, artemisinin had proven its amazing properties in killing cancer cells. (Singh and Verma, Case report of a laryngeal squamous cell carcinoma treated with artesunate, Archive of Oncology, Vol 10(4), 279-80, 2002)
TOXICITY OF ARTEMISININ - STUDY ON LARGE ANIMALS
Investigating if high doses of artemisinin could produce neurotixicity such as ding gait disturbances, loss of spinal and pain response, respiratory depression and ultimately cardiopulmonary arrest in large animals.
When artemisinin was given to monkey at 292 mg/kg over 1 to 3 months, they showed no toxicity. (Journal of Traditional Chinese Medicine 2(1) : 31-36, 1982)
In pharmacokinetic studies, 250 mg tablets of artemisin and artesunate tablets were used. Both forms of tablets were well tolerated and there were no negative side effects. (Benakis et al. Pharmacokinetics of artemisinin and artesunate after oral administration in healthy volunteers. American Journal of Tropical Medicine Hyg, Jan;56(1): 17-23, 1997)
During a study, healthy volunteers were given 250 mg of tablets of artemisinin and artesunate orally. Thee researchers reported that in the case of Artemisinin, the mean maximun drug concentration C= 0.36 microgram/ml, appearance half life T-0.62 hr, distribution hal life t(12) a= 2.61 hr, decline half life t(12) = 4.34 hr, total area under concentration curve (AUC) =1.10 microgram hg/ml its main metabolite, dihydroartemisinin was measured in plasma. On the other hand, half lives were more shorter in the case of artesunate (a syntetic form of the drug). (Benakis, et al, Dept of Pharmacology, Geneva U Swiss, Am J Trop Med Hyg, Jan; 56(1): 17-23, 1997.
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Publications Relating to Effects of Artemisinin and its Analogs on Cancer Cells
Beekman AC, Barentsen AR, Woerdenbag HJ, et al: Stereochemistry-dependent cytotoxicity of some artemisinin derivatives. J Nat Prod 60:325-330, 1997.
Beekman AC, Wierenga PK, Woerdenbag HJ, et al: Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells. Planta Med 64:615-619, 1998.
Beekman AC, Woerdenbag HJ, Van Uden W, et al: Stability of artemisinin in aqueous environments: impact on its cytotoxic action to Ehrlich ascites tumour cells. J Pharm Pharmacol 49:1254-1258, 1997.
Bhisutthibhan J, Philbert MA, Fujioka H, Aikawa M, Meshnick SR: The Plasmodium falciparum translationally controlled tumor protein: subcellular localization and calcium binding. Eur J Cell Biol 78:665-670, 1999.
Chen HH, Zhou HJ, Fang X: 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.
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, Davey M, Olbrich A, et al.: Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MDR1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells, Molecules, and Diseases 28:160-168, 2002.
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.
Fishwick J, Edwards G, Ward SA, et al: Binding of dihydroartemisinin to differentiating neuroblastoma cells and rat cortical homogenate. Neurotoxicology 19:405-412, 1998.
Fishwick J, Edwards G, Ward SA, et al: Morphological and immunocytochemical effects of dihydroartemisinin on differentiating NB2a neuroblastoma cells. Neurotoxicology 19:393-403, 1998.
Hu YQ, Tan RX, Chu MY, et al: Apoptosis in human hepatoma cell line SMMC-7721 induced by water-soluble macromolecular components of Artemisia capillaris Thunberg. Jpn J Cancer Res 91:113-117, 2000.
Lai H, Singh NP: Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Lett 91:41-46, 1995.
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.
Li Y, Shan F, Wu JM, et al: Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle. Bioorg Med Chem Lett 11:5-8, 2001.
McLean WG, Ward SA: In vitro neurotoxicity of artemisinin derivatives. Med Trop (Mars) 58:28-31, 1998.
Moore JC, Lai H, Li JR, et al: Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. Cancer Lett 98:83-87, 1995.
Mukanganyama S, Widersten M, Naik YS, et al: Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer 97:700-705, 2002.
Oh S, Jeong IH, Shin WS, Lee S: Growth inhibition activity of thioacetal artemisinin derivatives against human umbilical vein endothelial cells. Bioorg Med Chem Lett 3(21):3665-3668, 2003.
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.
Reungpatthanapong P, Mankhetkorn S: Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC/adr resistant cell lines. Biol Pharm Bull 25:1555-1561, 2002.
Sadava D, Phillips T, Lin C, et al: Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. Cancer Lett 179:151-156, 2002.
Shaikenov TE, Adekenov SM, Williams RM, et al: Arglabin-DMA, a plant derived sesquiterpene, inhibits farnesyltransferase. Oncol Rep 8:173-179, 2001.
Singh NP, Lai H: Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci 70:49-56, 2001.
Singh NP, Verma KB: Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 10:279-280, 2002.
Smith SL, Maggs JL, Edwards G, et al: The role of iron in neurotoxicity: a study of novel antimalarial drugs. Neurotoxicology 19:557-559, 1998.
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.
Woerdenbag HJ, Merfort I, Passreiter CM, et al: Cytotoxicity of flavonoids and sesquiterpene lactones from Arnica species against the GLC4 and the COLO 320 cell lines. Planta Med 60:434-437, 1994.
Woerdenbag HJ, Moskal TA, Pras N, et al: Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 56:849-856, 1993.
Wu JM, Shan F, Wu GS, et al: Synthesis and cytotoxicity of artemisinin derivatives containing cyanoarylmethyl group. Eur J Med Chem 36:469-479, 2001.
Zheng GQ: Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med 60:54-57, 1994.
Artemisinin Pharmacology and Pharmacokinetics
Dhingra V, Rao KV, Narasu NL: Current status of artemisinin and its derivatives as antimalarial drugs. Life Sci 66:279-300, 2000.
Li Y, Wu YL: An over four millennium story behind qinghaosu (artemisinin--a fantastic antimalarial drug from a traditional chinese herb). Curr Med Chem 10(21):2197-2230, 2003.
Navaratnam V, Mansor SM, Sit NW, et al: Pharmacokinetics of artemisinin-type compounds. Clin Pharmacokinet 39:255-270, 2000.