Abstract
The human aldo–keto reductase AKR1B10, originally identified as an aldose reductase-like protein and human small intestine aldose reductase, is a cytosolic NADPH-dependent reductase that metabolizes a variety of endogenous compounds, such as aromatic and aliphatic aldehydes and dicarbonyl compounds, and some drug ketones. The enzyme is highly expressed in solid tumors of several tissues including lung and liver, and as such has received considerable interest as a relevant biomarker for the development of those tumors. In addition, AKR1B10 has been recently reported to be significantly up-regulated in some cancer cell lines (medulloblastoma D341 and colon cancer HT29) acquiring resistance toward chemotherapeutic agents (cyclophosphamide and mitomycin c), suggesting the validity of the enzyme as a chemoresistance marker. Although the detailed information on the AKR1B10-mediated mechanisms leading to the drug resistance process is not well understood so far, the enzyme has been proposed to be involved in functional regulations of cell proliferation and metabolism of drugs and endogenous lipids during the development of chemoresistance. This article reviews the current literature focusing mainly on expression profile and roles of AKR1B10 in the drug resistance of cancer cells. Recent developments of AKR1B10 inhibitors and their usefulness in restoring sensitivity to anticancer drugs are also reviewed.
Highlights
The aldo–keto reductase (AKR) superfamily is a rapidly growing group of NAD(P)(H)-dependent oxidoreductases that metabolize carbohydrates, steroids, prostaglandins, and other endogenous aldehydes and ketones, as well as xenobiotic compounds
We show evidence that the modulation of the isoprenoid metabolism by AKR1B10 is involved in proliferative capacity of the L-OHP-resistant HT29 cells (Figures 5 and 6)
CONCLUDING REMARKS It is commonly assumed that chemoresistance of cancer cells is induced with extraordinary enhancement of four capacities (1)
Summary
The aldo–keto reductase (AKR) superfamily is a rapidly growing group of NAD(P)(H)-dependent oxidoreductases that metabolize carbohydrates, steroids, prostaglandins, and other endogenous aldehydes and ketones, as well as xenobiotic compounds (http://www.med.upenn.edu/akr/). Members of this superfamily are classified into 15 families, and each family is subdivided into several subfamilies based on their amino acid sequence similarities. Human aldose reductase-like protein AKR1B10 has been recently regarded as a potential diagnostic and/or prognostic marker in carcinomas and serum (Fukumoto et al, 2005; Luo et al, 2011), and as a therapeutic target for the prevention and treatment of several types of cancer (Liu et al, 2009a). We provide an update on the usefulness of AKR1B10 inhibitors in restoring sensitivity to anticancer drugs
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