RRC ID 43540
著者 Simamura E, Shimada H, Ishigaki Y, Hatta T, Higashi N, Hirai K.
タイトル Bioreductive activation of quinone antitumor drugs by mitochondrial voltage-dependent anion channel 1.
ジャーナル Anat Sci Int
Abstract The authors recently demonstrated that the mitochondrial voltage-dependent anion channel 1 (VDAC1) is involved in the sensitivity of cancer cells to furanonaphthoquinone (FNQ). The aim of the present study was to investigate whether mitochondrial VDAC1 reduces quinone antitumor drugs. The VDAC1 purified by immunoprecipitation reduced FNQ in the presence of nicotinamide adenine dinucleotide (NADH) and produced H(2)O(2). Blue native polyacrylamide gel electrophoresis demonstrated that the band that reduced FNQ NADH-dependently mainly included VDAC1. Because H(2)O(2) generation in catalyzing FNQ with NADH caused mitochondrial damage, the cytotoxic activity of FNQ was induced by VDAC1. In the quinone antitumor drugs, menadione (VK3), adriamycin and mitomycin C, mitochondrial VDAC1 bioreductively activated VK3. These results demonstrate that mitochondrial VDAC1 is a pharmacologic target for the treatment of tumor.
巻・号 83(4)
ページ 261-6
公開日 2008-12-1
DOI 10.1111/j.1447-073X.2008.00241.x
PII ASI241
PMID 19159355
MeSH Antineoplastic Agents / metabolism* Apoptosis / physiology Cell Line Doxorubicin / metabolism HeLa Cells Humans Hydrogen Peroxide / metabolism Mitochondria / metabolism* Mitomycin / metabolism NAD / metabolism Naphthoquinones / metabolism* Oxidation-Reduction Quinones / metabolism* Vitamin K 3 / metabolism Voltage-Dependent Anion Channel 1 / metabolism*
IF 1.512
引用数 23
WOS 分野 ANATOMY & MORPHOLOGY DEVELOPMENTAL BIOLOGY
リソース情報
ヒト・動物細胞 HeLa(RCB0007)