BioEngineering

Artemisinin

IMPORTANT NOTE: The Department of Bioengineering and University of Washington do not advocate the use of artemisinin to treat cancer. The US Food and Drug Administration does not currently approve the use of artemisinin for the treatment of any disease. Research on artemisinin and cancer is still in very early stages. Human use of artemisinin should be considered experimental and taking artemisinin or any other drug should be approached with extreme caution and responsibility.

ALWAYS CONSULT WITH YOUR PHYSICIAN BEFORE BEGINNING ANY NEW THERAPY OR TREATMENT

Below is a list of publications covering the research being done by UW and other institutions on artemisinin and cancer. The list is organized into two categories: publications related to the effects of artemisinin and its analogs on cancer and artemisinin pharmacology and pharmacokinetics. You may find them useful when consulting with your personal physician. We have also compiled a comprehensive list of artemisinin-related articles (more than 350 publications) that you may also find useful.

Publications Relating to Effects of Artemisinin and its Analogs on Cancer

  1. Li LN et al. Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/beta-catenin pathway. Int J Cancer. 121(6):1360-1365, 2007.
  2. Mu D et al. The role of calcium, P38 MAPK in dihydroartemisinin-induced apoptosis of lung cancer PC-14 cells. Cancer Chemother Pharmacol. 2007 Jul 4; [Epub ahead of print]
  3. Efferth T et al. From traditional Chinese medicine to rational cancer therapy. Trends Mol Med. 2007 Jul 16; [Epub ahead of print]
  4. Jiao Y et al. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin. 28(7):1045-1056, 2007.
  5. Huang XJ et al. Dihydroartemisinin exerts cytotoxic effects and inhibits hypoxia inducible factor-1alpha activation in C6 glioma cells. J Pharm Pharmacol. 59(6):849-856, 2007.
  6. Nam W et al. Effects of artemisinin and its derivatives on growth inhibition and apoptosis of oral cancer cells. Head Neck. 29(4):335-340, 2007.
  7. Efferth T. Willmar Schwabe Award 2006: Antiplasmodial and Antitumor Activity of Artemisinin - From Bench to Bedside. Planta Med. 2007 Mar 12.
  8. Wang JX et al. Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation. Br J Pharmacol. 150(5):652-661, 2007.
  9. Wang JX et al. Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo. Eur J Pharmacol. 564:211-218, 2007.
  10. Utzinger J et al. Artemisinins for schistosomiasis and beyond. Curr Opin Investig Drugs. 8(2):105-116, 2007.
  11. Xu H et al. Anti-malarial agent artesunate inhibits TNF-{alpha}-induced production of proinflammatory cytokines via inhibition of NF-{kappa}B and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes. Rheumatology ( Oxford). 46:920-926, 2007.
  12. Mu D et al. Calcium and survivin are involved in the induction of apoptosis by dihydroartemisinin in human lung cancer SPC-A-1 cells. Methods Find Exp Clin Pharmacol. 29(1):33-38, 2007.
  13. Withers ST and Keasling JD. Biosynthesis and engineering of isoprenoid small molecules. Appl Microbiol Biotechnol. 73(5):980-990, 2007.
  14. Mercer AE et al. Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J Biol Chem. 282:9372-9382, 2007
  15. Singh NP and Panwar VK Case report of a pituitary macroadenoma treated with artemether. Integr Cancer Ther. 5(4):391-394, 2006.
  16. Golenser J et al. Current perspectives on the mechanism of action of artemisinins. Int J Parasitol. 36(14):1427-1441, 2006.
  17. Romero MR et al. Antiviral effect of artemisinin from Artemisia annua against a model member of the Flaviviridae family, the bovine viral diarrhoea virus (BVDV). Planta Med. 72(13):1169-1174, 2006.
  18. Wiwanitkit V. Quantum chemical analysis of alternative pathways for iron activation step for artemisinin, a new antimalarial drug. J Infect. 53(3):148-151, 2006. .
  19. Li W et al. Yeast model uncovers dual roles of mitochondria in action of artemisinin. PLoS Genet. 1(3):e36, 2005.
  20. Wu XH et al. Dihydroartemisinin inhibits angiogenesis induced by multiple myeloma RPMI8226 cells under hypoxic conditions via downregulation of vascular endothelial growth factor expression and suppression of vascular endothelial growth factor secretion. Anticancer Drugs. 17(7):839-848, 2006.
  21. Anfosso L et al. Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J. 6(4):269-278, 2006.
  22. Paik IH et al. Second generation, orally active, antimalarial, artemisinin-derived trioxane dimers with high stability, efficacy, and anticancer activity. J Med Chem. 49(9):2731-2734, 2006.
  23. Efferth T. Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr Drug Targets. 7(4):407-421, 2006.
  24. Ro DK et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature. 440(7086):940-943, 2006.
  25. Kim SJ et al. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol. 132(2):129-135, 2006.
  26. Kaptein SJ et al. The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo. Antiviral Res. 69(2):60-69, 2006.
  27. Lai, H and Singh, NP. Oral artemisinin prevents and delays the development of 7, 12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in the rat. Cancer Letters. 231(1):43-48, 2006.
  28. Lee J et al. Dihydroartemisinin downregulates vascular endothelial growth factor expression and induces apoptosis in chronic myeloid leukemia K562 cells. Cancer Chemother Pharmacol. 57(2):213-220, 2006.
  29. Disbrow GL et al. Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo. Cancer Research. 65(23):10854-10861, 2005.
  30. Berger TG et al. Artesunate in the treatment of metastatic uveal melanoma--first experiences. Oncol Rep. 14(6):1599-603, 2005.
  31. Singh N.P. and Lai H. Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells. Anticancer Research. 25(6B):4325-4231, 2005.
  32. Romero MR et al. Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system. Antiviral Res. 68(2):75-83, 2005.
  33. Li J and Zhou HJ. Dihydroartemisinin inhibits the expression of vascular endothelial growth factor in K562 cells [Article in Chinese]. Yao Xue Xue Bao. 240(11):1041-1045, 2005.
  34. Lai, H., Sasaki, T. and Singh, N.P. Targeted treatment of cancer with artemisinin and artemisinin-tagged iron-carrying compounds. Expert Opin Ther Targets. 9(5):995-1007, 2005.
  35. Liu Y et al. Synthesis and cytotoxicity studies of artemisinin derivatives containing lipophilic alkyl carbon chains. Org Lett. 7(8):1561-1564, 2005.
  36. Efferth T. Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. Drug Resist Update. 8(1-2):85-97, 2005.
  37. Efferth T and Volm M. Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. In Vivo. 19(1):225-232, 2005.
  38. Lai, H., Sasaki, T., Singh, N.P., and Massey A. Effects of artemisinin-tagged holotransferrin on cancer cells. Life Sciences 76:1267-1279, 2005.
  39. Dell'Eva R. et al. Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate. Biochem Pharmacol. 68(12):2359-2366, 2004.
  40. Efferth T. et al. Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radic Biol Med. 37(7):998-1009, 2004.
  41. Singh N.P. and Lai H. Artemisinin induces apoptosis in human cancer cells. Anticancer Research 24:2277-2280, 2004.
  42. Yamachika E, Habte T, and Oda D. Artemisinin: an alternative treatment for oral squamous cell carcinoma. Anticancer Res. 24(4):2153-2160, 2004.
  43. Oh S et al. Synthesis and antiangiogenic activity of thioacetal artemisinin derivatives. Bioorg Med Chem. 12(14):3783-3790, 2004.
  44. Efferth T. and Oesch F. Oxidative stress response of tumor cells: microarray-based comparison between artemisinins and anthracyclines. Biochem Pharmacol. 68(1):3-10, 2004.
  45. Chen H.H. et al. Inhibitory effects of artesunate on angiogenesis and on expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1. Pharmacology. 71(1):1-9, 2004.
  46. Efferth T et al. Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774. Biochem Pharmacol. 67(9):1689-1700, 2004.
  47. Huan-Huan C et al. Artesunate reduces chicken chorioallantoic membrane neovascularisation and exhibits antiangiogenic and apoptotic activity on human microvascular dermal endothelial cell. Cancer Lett 211(2):163-73, 2004.
  48. Posner G.H. et al. Anticancer and antimalarial efficacy and safety of artemisinin-derived trioxane dimers in rodents. J Med Chem. 47(5):1299-1301, 2004.
  49. Jeyadevan J.P. et al. Antimalarial and antitumor evaluation of novel C-10 non-acetal dimers of 10beta-(2-hydroxyethyl) deoxoartemisinin. J Med Chem. 47(5):1290-1298, 2004.
  50. Kim S.H. et al. Differential involvement of protein kinase C in human promyelocytic leukemia cell differentiation enhanced by artemisinin. Eur J Pharmacol. 482(1-3):67-76, 2003.
  51. Wartenberg M et al. The antimalaria agent artemisinin exerts antiangiogenic effects in mouse embryonic stem cell-derived embryoid bodies. Lab Invest. 83(11):1647-1655, 2003.
  52. Oh S et al. Growth inhibition activity of thioacetal artemisinin derivatives against human umbilical vein endothelial cells. Bioorg Med Chem Lett. 13(21):3665-3668, 2003.
  53. McCarty M.F. Turning an 'Achilles' Heel' into an asset--activation of HIF-1alpha during angiostatic therapy will increase tumor sensitivity to iron-catalyzed oxidative damage. Med Hypotheses. 61(4):509-511, 2003.
  54. Efferth T et al. Role of antioxidant genes for the activity of artesunate against tumor cells. Int J Oncol. 23(4):1231-1235, 2003.
  55. Chen H.H. et al. Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro. Pharmacol Res. 48(3):231-236, 2003.
  56. Aldieri E et al. Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation. FEBS Lett. 552(2-3):141-144, 2003.
  57. Posner G.H. et al. Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy. J Med Chem. 46(6):1060-1065, 2003.
  58. Reungpatthanaphong P and Mankhetkorn S. Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines. Biol Pharm Bull. 25(12):1555-1561, 2002.
  59. Efferth T et al. mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether. Biochem Pharmacol. 64(4):617-623, 2002.
  60. Sadava D et al. Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. Cancer Letters. 179(2):151-156, 2002.
  61. Singh N.P. and Verma K.B. Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 10:279-280, 2002.
  62. Efferth T et al. Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses. J Mol Med. 80(4):233-242, 2002.
  63. Efferth T et al. Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells Mol Dis. 28(2):160-168, 2002.
  64. Mukanganyama S et al. Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer 97:700-705, 2002.
  65. Singh, N.P. and Lai, H. Selective toxicity of dihydroartemisinin and holotransferrin on human breast cancer cells. Life Sciences 70:49-56, 2001.
  66. Efferth T et al. The anti-malarial artesunate is also active against cancer. Int J Oncol. 18(4):767-773, 2001.
  67. Li Y et al. Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle. Bioorg Med Chem Lett 11:5-8, 2001.
  68. Hu YQ 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.
  69. Lee CH et al. NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin. Biochem Biophys Res Comm 274:359-369, 2000.
  70. Beekman AC et al. Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells. Planta Med 64:615-619, 1998.
  71. Beekman AC et al. Stereochemistry-dependent cytotoxicity of some artemisinin derivatives. J Nat Prod 60:325-330, 1997.
  72. Beekman AC 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.
  73. Moore J.C. et al. Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. Cancer Letters 98:83-87, 1995.
  74. Lai, H. and Singh, N.P. Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Letters 91:41-46, 1995.
  75. Woerdenbag HJ 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.
  76. Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med 60:54-57, 1994.
  77. Woerdenbag HJ et al. Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 56:849-856, 1993.
  78. Deng DA et al. Derivatives of arteannuin B with antileukemia activity [Article in Chinese]. Yao Xue Xue Bao. 27(4):317-320, 1992.
  79. Sun WC et al. Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro [Article in Chinese]. Zhongguo Yao Li Xue Bao 13:541-543, 1992.

Artemisinin Pharmacology and Pharmacokinetics

  1. Dhingra V, Rao KV, Narasu NL: Current status of artemisinin and its derivatives as antimalarial drugs. Life Sci 66:279-300, 2000.
  2. 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.
  3. Navaratnam V, Mansor SM, Sit NW, et al: Pharmacokinetics of artemisinin-type compounds. Clin Pharmacokinet 39:255-270, 2000.