The anti-malarial artesunate is also active against cancer. Int J Oncol 2001 Apr;18(4):767-73
Date
03/17/2001Pubmed ID
11251172DOI
10.3892/ijo.18.4.767Scopus ID
2-s2.0-0035315838 (requires institutional sign-in at Scopus site) 547 CitationsAbstract
Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. ART has now been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines (mean GI50 values: 1.11+/-0.56 microM and 2.13+/-0.74 microM , respectively). Non-small cell lung cancer cell lines showed the highest mean GI50 value (25.62+/-14.95 microM) indicating the lowest sensitivity towards ART in this test panel. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. Importantly, a comparison of ART's cytotoxicity with those of other standard cytostatic drugs showed that ART was active in molar ranges comparable to those of established anti-tumor drugs. Furthermore, we tested CEM leukemia sub-lines resistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea which do not belong to the N.C.I. screening panel. None of these drug-resistant cell lines showed cross resistance to ART. To gain insight into the molecular mechanisms of ART's cytotoxicity, we used a panel of isogenic Saccaromyces cerevisiae strains with defined genetic mutations in DNA repair, DNA checkpoint and cell proliferation genes. A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644. None of the other DNA repair or DNA check-point deficient isogenic strains were different from the wild-type. These results and the known low toxicity of ART are clues that ART may be a promising novel candidate for cancer chemotherapy.
Author List
Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CRMESH terms used to index this publication - Major topics in bold
AntimalarialsAntineoplastic Agents
Artemisinins
Cell Cycle Proteins
Cell Division
Cyclin G
Cyclin G1
Cyclins
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Fluorescent Dyes
Humans
Leukemia
Neoplasms
Poly-ADP-Ribose Binding Proteins
Proteins
Rhodamines
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Sesquiterpenes
Tumor Cells, Cultured