Journal
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Volume 24, Issue 2, Pages 110-112Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2010.12.005
Keywords
Nitric oxide; Nitric oxide synthase; Artesunate; Cancer
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Funding
- Natural Science Foundation of Guangdong China [9145624536-4000003]
- Scientific Development Project of Guangdong China [2007B031404008]
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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 (A(415)) to the ART-heme adduct (A(476)). Accordingly, a transient elevation of A(415) was observed with a synchronous burst of nitric oxide (NO) and a high rate of survival following incubation of HepG2 with 50 mu M ART. In contrast, ART at above 100 mu M 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. (C) 2010 Elsevier Inc. All rights reserved.
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