title: Involvement of the aldo-keto reductase, AKR1B10, in mitomycin-c resistance through reactive oxygen species-dependent mechanisms.
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.
authors.affiliation: Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, Japan. matsunagat@gifu-pu.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamane
authors.forename: Keiko
authors.initials: K
authors.lastname: Iida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Banno
authors.forename: Ossama
authors.initials: O
authors.lastname: El-Kabbani
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology; D000074408:Aldo-Keto Reductases; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D015227:Lipid Peroxidation; D016685:Mitomycin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000447:Aldehydes; D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016685:Mitomycin; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D053148:Caspase 3; C027576:4-hydroxy-2-nonenal