期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 512, 期 2, 页码 160-166出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2011.06.004
关键词
MRP2; Genistein; Resveratrol; Cancer chemopreventive phytochemical; RXR alpha
资金
- National Institute of Health [R01 CA73674]
The interactions between various dietary cancer chemopreventive phytochemicals in drug transporter functions are not well studied. In this study, the effects of genistein and resveratrol on the multidrug resistance protein 2 (MRP2) expression and the underlying molecular mechanisms were investigated using HepG2-C3 cells that are stably transfected with a construct containing human MRP2 promoter region conjugated with luciferase reporter gene. A 3-fold induction of MRP2 luciferase activity was observed after genistein (50 mu M) treatment to HepG2-C3 cells, but was diminished by the resveratrol (50 mu M) cotreatment. This observation was further validated by Western blot analysis and RT-PCR analysis as resveratrol also inhibited genistein-induced MRP2 protein synthesis and mRNA expression. Immunofluorescence study revealed that genistein-induced formation of MRP2 vacuoles was dramatically reduced by resveratrol. The binding affinity between retinoid X receptor alpha (RXR alpha) and MRP2 promoter was examined by DNA-protein pull-down assay. The results showed that resveratrol inhibited the genistein-induced binding of RXR alpha to the promoter sequence of MRP2 gene, and this mechanism could potentially contribute to the inhibition of genistein-induced MRP2 expression by resveratrol. Taken together, our present study suggests that naturally occurring phytochemicals can potentially interfere with each other's regulatory function on the cancer chemoprevention-related genes through a competitive mechanism. (C) 2011 Elsevier Inc. All rights reserved.
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