Involvement of the aldo-keto reductase, AKR1B10, in mitomycin-c resistance through reactive oxygen species-dependent mechanisms

Toshiyuki Matsunaga, Yumi Yamane, Lida Keiko, Satoshi Endo, Yoshiko Banno, Ossama El-Kabbani, Akira Hara

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30 Citations (Scopus)

Abstract

The human aldo-keto reductase (AKR) 1B10 is suggested as a tumor marker in various solid tumors. Using colon cancer cells, we found that AKR1B10 was induced with acquisition of resistance to the anticancer drug mitomycin-c (MMC). In the resistant cells, treatment with an AKR1B10 inhibitor decreased their MMC tolerance. In the nonresistant cells, overexpression and silencing of AKR1B10 decreased and increased, respectively, susceptibility to cytotoxic effects of MMC and 4-hydroxy-2-nonenal, which was formed as a product of lipid peroxidation by MMC treatment. These results suggest a role of AKR1B10 in the development of MMC resistance, which may be mediated by its ability to detoxify cytotoxic aldehydes including 4-hydroxy-2-nonenal. Anti-Cancer Drugs 22:402-408 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams Wilkins.
Original languageEnglish
Pages (from-to)402 - 408
Number of pages7
JournalAnti-Cancer Drugs
Volume22
Issue number5
DOIs
Publication statusPublished - 2011

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