The anti-malarial artesunate is also active against cancer

Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activ ity against otherwise multidrug-resistant Plasmodium falciparum and P. viva x malaria. ART has now been analyzed for its anticancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cance r Institute, USA. ART was most active against leukemia and colon cancer cel l lines (mean GI(50) values: 1.11 +/-0.56 muM and 2.13 +/-0.74 muM, respect ively). Non-small cell lung cancer cell lines showed the highest mean GI(50 ) value (25.62 +/- 14.95 muM) indicating the lowest sensitivity towards NIT in this test panel. Intermediate GI(50) 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 es tablished anti-tumor drugs. Furthermore, we tested CEM leukemia sub-lines r esistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea w hich do not belong to the N.C.I, screening panel. None of these drug-resist ant cell lines showed cross resistance to ART. To gain insight into the mol ecular mechanisms of ART's cytotoxicity, we used a panel of isogenic Saccar omyces cerevisiae strains with defined genetic mutations in DNA repair, DNA checkpoint and cell proliferation genes. A yeast strain with a defective m itosis regulating BUB3 gene showed increased ART sensitivity and another st rain with a defective proliferation-regulating CLN2 gene showed increased A RT resistance over the wild-type strain, wt644. None of the other DNA repai r or DNA check-point deficient isogenic strains were different from the wil dtype. These results and the known low toxicity of ART are clues that ART m ay be a promising novel candidate for cancer chemotherapy.