title: Cytotoxicity of dihydroartemisinin toward Molt-4 cells attenuated by N-tert-butyl-alpha-phenylnitrone and deferoxamine.
abstract: Derivatives of artemisinin, a compound extracted from the wormwood Artemisia annua L, have potent anticancer properties. The anticancer mechanisms of artemisinin derivatives have not been fully-elucidated. We hypothesize that the cytotoxicity of these compounds is due to the free radicals formed by interaction of their endoperoxide moiety with intracellular iron in cancer cells. The effects of N-tert-butyl-alpha-phenylnitrone (PBN), a spin-trap free radical scavenger, and deferoxamine (DX), an iron chelating agent, on the in vitro cytotoxicity of dihyroartemisinin (DHA) toward Molt-4 human T-lymphoblastoid leukemia cells were investigated in the present study. Dihydroartemisinin effectively killed Molt-4 cells in vitro. Its cytotoxicity was significantly attenuated by PBN and DX. Based on the data of our present and previous studies, we conclude that one anticancer mechanism of dihydroartemisinin is the formation of toxic-free radicals via an iron-mediated process.
authors.affiliation: Department of Bioengineering, Box 355061, University of Washington, Seattle, WA 98195-5061, U.S.A. Narendra@u.washington.edu.
authors.forename: Ho Wing
authors.initials: HW
authors.lastname: Chan
authors.forename: Narendra P
authors.initials: NP
authors.lastname: Singh
authors.forename: Henry C
authors.initials: HC
authors.lastname: Lai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D004336:Drug Antagonism; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D017262:Siderophores / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D017262:Siderophores; C029217:phenyl-N-tert-butylnitrone; C039060:artenimol; D003676:Deferoxamine
keywords: Dihydroartemisinin; Molt-4 cells; N-tert-butyl-alpha-phenylnitrone; deferoxamine; free radical; iron