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: Eriko Simamura, Hiroki Shimada, Yasuhito Ishigaki, Toshihisa Hatta, Nobuaki Higashi, Kei-Ichi Hirai
• Journal: Anatomical science international (Anat Sci Int) Vol. 83 Issue 4 Pg. 261-6 (Dec 2008) ISSN: 1447-6959 [Print] Japan
• PMID: 19159355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-methyl-8-hydroxynaphtho(2,3-b)furan-4,9-dione
• Antineoplastic Agents
• Naphthoquinones
• Quinones
• VDAC1 protein, human
• NAD
• Mitomycin
• Vitamin K 3
• Doxorubicin
• Hydrogen Peroxide
• Voltage-Dependent Anion Channel 1

Topics

• 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)