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Artemisinina Antineoplásica 

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 científicos demuestran que la artemisinina también es una potente arma contra el cáncer. La artemisina posee acción citotóxica selectiva contra las células de cáncer sobrecargadas de hierro (Las células de cáncer presentan más receptores de hierro y mayor contenido de hierro intracelular que las células normales). La artemisinina es un endoperoxida (agente con fuerte acción oxidativa) que tiene una gran afinidad por el hierro intracelular, y precisamente mediante ese mecanismo es que se aloja selectivamente en las células cancerosas y las destruye por reacción oxidativa.

La administración de la Artemisinina: La artemisinina comúnmente se administra vía oral, intramuscular o endovenosa. La absorción gastrointestinal de la artemisisnina oral disminuye considerablemente después de dos a tres días de administración continua. Por lo que la artemisinina oral es más apropiada para pacientes con malaria. El uso de la artemisinina para terapia antitumoral requiere una dosis mayor que la dosis que comúnmente se administra a pacientes con malaria. La dosificación de la artemisinina se realiza de acuerdo al peso corporal del paciente, y la vía de administración para pacientes con cáncer debe ser mediante infusión endovenosa o inyección intramuscular (algunos casos también han respondido bien a la artemisinina vía intratumoral o a una combinación intratumoral y sistémica).

La artemisinina posse una fuerte acción antitumoral y efectos secundarios muy minimos y facilmente manejables. Sin embargo, durante un tratamiento intensivo con artemisinina, el paciente debe estar bajo observación médica, preferiblemente en un hospital o centro médico apropiado. 

El Dr. Marcelo Lam es uno de los médicos con más conocimiento y experiencia en la administración de la artemisina en pacientes con cáncer. La artemisinina se puede administrar de forma exclusiva o en combinación con tratamientos convencionales. En China, la artemisinina está disponible en combinación con Gendicine y Oncorine (H101) (terapia genética antitumoral), crío-ablación, HIFU, hipertermia, y otros procedimientos. 

Nuestro programa internacional de oncología integrada cuenta con un equipo de eminentes médicos aliados en los Estados Unidos, China, y Republica Dominicana, que en un esfuerzo mancomunado provee excelencia en tratamientos integrados contra el cáncer.
 

 

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)

ANTI-TUMOR EFFECT
When artemisinin's derivative, 9 C-10 was prepared as dimers using novel chemistry, it proved to be able to kill malaria cells. Additionally, dimers 8, 10 and 12 were especially powerful and prevented cancer growth in the NCI in vitro 60 cell line assay.   (Posner, GH et al, Antimalarial, antiproliferative and antitumor activities of Artemisin Derived Dimers, J Medicinal Chemistry, 42(21), 178-181, Oct 1999)

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)

TUMOR CELLS
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) 

HEALTHY VOLUNTEERS
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)

PHARMACOKINETICS
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.   

TCM Imperial Pharmacy™ and TCM Physicians Clinic are dedicated to bring the best of Traditional Chinese Medicine and new discoveries in herbal remedies for the health benefit of humankind.

Published Articles Relating to the Effects of Artemisinin and its Analogs on Cancer Cells:

  1. Tu Y (2011) The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med 17(10):1217–1220 
    Cancer   PubMed     CrossRef              

  1. Lai H, Singh NP (1995) Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Lett 91:41–46   
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    PubMed  CrossRef      Google Scholar


  1. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR (2001) The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767–773  
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  1. König M, von Hagens C, Hoth S, Baumann I, Walter-Sack I, Edler L et al (2016) Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study. Cancer Chemother Pharmacol 77(2):413–427. doi:10.1007/s00280-016-2960-7
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  1. Singh NP, Verma KB (2002) Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch. Oncol 10(4):279–280
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  1. Singh NP, Panwar VK (2006) Case Report of a Pituitary Macroadenoma Treated With Artemether. Integr Cancer Ther 5(4):391–394
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  1. Rowen RJ (2002) Artemisinin: from Malaria to cancer treatment. Townsend Letter for Doctors & Patients pp 86–88

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  1. Wu M-X (2016) Effect of artemisinin combined with cisplatin intervention on epithelial-mesenchymal transition, angiogenesis and ATP generation in MGC-803 gastric cancer cell lines. J Hainan Med Univer 22(18) (Abstract only available, article in Chinese)

  1. Wang B, Hou D, Liu Q, Wu T, Guo H, Zhang X et al (2015) Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer Biol Ther 16(10):1548–1556. doi:10.1080/15384047.2015.1071738
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  1. Tran KQ, Tin AS, Firestone GL (2014) Artemisinin triggers a G1 cell cycle arrest of human Ishikawa endometrial cancer cells and inhibits cyclin-dependent kinase-4 promoter activity and expression by disrupting nuclear factor-κB transcriptional signaling. Anticancer Drugs 25(3):270–281. doi:10.1097/CAD.0000000000000054PubMed
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