Iron‐dependent hydroxyl radical formation and DNA damage from a novel metabolite of the clinically active antitumor drug VP‐16

FEBS Letters

Kalayanaraman, B.¹  Sinha, Birandra K.²  Eliot, Helen M.² 

[1] Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;Clinical Oncology Program, Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

关键词: VP-16;    VP-16 catechol metabolite;    Iron complex;    Hydroxyl radical;    Spin trapping;   

DOI  :  10.1016/0014-5793(88)80906-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The dihydroxy derivative of VP-16 (DHVP), a novel metabolite of the clinically active antitumor drug VP-16, was cytotoxic to human breast tumor cells. It was found that DHVP chelates iron and catalyzes the formation of hydroxyl radicals from hydrogen peroxide and reduced glutathione. Ethanol, polyethylene glycol and t-butanol inhibited the formation of DMPO-OH, suggesting that perferryl iron was not involved in OH^. formation. Under conditions which formed hydroxyl radicals, DHVP also induced nicking of SV40 DNA, suggesting that the mechanism of tumor cell killing by DHVP may involve iron-dependent free radical formation.

【 授权许可】

Unknown