title: Artesunate mitigates proliferation of tumor cells by alkylating heme-harboring nitric oxide synthase.
abstract: Artesunate (ART), a semi-synthetic derivative of antimalarial artemisinin, kills cancer cells with uncertain mechanisms. Here, we report for the first time that ART may exert the anti-tumor activity by conjugating the prosthetic heme of hemoproteins in a hepatoma cell line, HepG2, which was evident by monitoring the shift of absorbance from heme (A₄₁₅) to the ART-heme adduct (A₄₇₆). Accordingly, a transient elevation of A₄₁₅ was observed with a synchronous burst of nitric oxide (NO) and a high rate of survival following incubation of HepG2 with 50 μM ART. In contrast, ART at above 100 μM led to an abrogation of NO generation and a decline of the survival rate in HepG2. These data implied that heme-containing nitric oxide synthase (NOS) may represent a major cellular target of ART in killing tumor cells.
authors.affiliation: Laboratory of Biotechnology, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, 510405 Guangzhou, China. qpzeng@163.com
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Zeng
authors.forename: Ping-Zu
authors.initials: PZ
authors.lastname: Zhang
mesh_terms: D000478:Alkylation; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006418:Heme / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000378:metabolism*; D013053:Spectrophotometry
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D006418:Heme; D000077332:Artesunate; D019001:Nitric Oxide Synthase