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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Reductase / antagonists & inhibitors
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Aldehyde Reductase / biosynthesis
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Aldehyde Reductase / genetics
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Aldehyde Reductase / metabolism*
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Aldehydes / metabolism
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Aldehydes / pharmacology
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Aldo-Keto Reductases
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Antibiotics, Antineoplastic / pharmacology
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Caspase 3 / metabolism
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Drug Resistance, Neoplasm
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Drug Synergism
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Gene Knockdown Techniques
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HT29 Cells
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Humans
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Lipid Peroxidation
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Mitomycin / pharmacology*
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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RNA, Small Interfering / administration & dosage
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RNA, Small Interfering / genetics
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Reactive Oxygen Species / metabolism*
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Tumor Cells, Cultured
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Up-Regulation
Substances
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Aldehydes
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Antibiotics, Antineoplastic
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RNA, Messenger
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RNA, Small Interfering
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Reactive Oxygen Species
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Mitomycin
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AKR1B10 protein, human
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Aldo-Keto Reductases
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Aldehyde Reductase
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Caspase 3
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4-hydroxy-2-nonenal