title: Bioreductive activation of quinone antitumor drugs by mitochondrial voltage-dependent anion channel 1.
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.
authors.affiliation: Department of Molecular and Cell Structural Science, Kanazawa Medical University, Uchinada, Japan. simamura@kanazawa-med.ac.jp
authors.forename: Eriko
authors.initials: E
authors.lastname: Simamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimada
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Hatta
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Higashi
authors.forename: Kei-Ichi
authors.initials: K
authors.lastname: Hirai
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D004317:Doxorubicin / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D016685:Mitomycin / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009285:Naphthoquinones / Q000378:metabolism*; D010084:Oxidation-Reduction; D011809:Quinones / Q000378:metabolism*; D024483:Vitamin K 3 / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
chemical_list: C111775:2-methyl-8-hydroxynaphtho(2,3-b)furan-4,9-dione; D000970:Antineoplastic Agents; D009285:Naphthoquinones; D011809:Quinones; C494762:VDAC1 protein, human; D009243:NAD; D016685:Mitomycin; D024483:Vitamin K 3; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D050995:Voltage-Dependent Anion Channel 1