Resveratrol inhibits genistein-induced multi-drug resistance protein 2 (MRP2) expression in HepG2 cells.

Abstract:

: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 (50μM) treatment to HepG2-C3 cells, but was diminished by the resveratrol (50μM) 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 (RXRα) and MRP2 promoter was examined by DNA-protein pull-down assay. The results showed that resveratrol inhibited the genistein-induced binding of RXRα 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.

journal_name

Arch Biochem Biophys

authors

Kim JH,Chen C,Tony Kong AN

doi

10.1016/j.abb.2011.06.004

subject

Has Abstract

pub_date

2011-08-15 00:00:00

pages

160-6

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(11)00215-3

journal_volume

512

pub_type

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