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Sulforaphane modulates MRP expression and activity in Caco-2 cells

Katarzyna Lubelska 1Ilona Zbroińska 1Małgorzata Milczarek 1,2Dariusz Matosiuk 2Zdzisław Chilmonczyk 1Katarzyna Wiktorska 1

1. National Medicines Institute (NIL), Chełmska 30/34, Warszawa 00-725, Poland
2. Medical University, Faculty of Pharmacy, Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Staszica 6, Lublin 20-081, Poland

Abstract

 Sulforaphane (SFN) is a chemopreventive isothiocyanate (ITC) found in vegetables from the Brassica family. SFN has been already shown to be inducer not only of metabolism phase 2 detoxification enzymes but also of  phase 3 detoxification enzymes, which include, among others transport proteins like MRP (multidrug resistance-associated protein). The accumulation of products of the metabolism phase 2 enzymes may lead to reduced activity of detoxification system. Therefore, the metabolism phase 3 detoxification enzymes involved in carcinogen  transport across the cell membrane finally eliminate the xenobiotics from the cell. Thus, the metabolism both phases (2 and 3) contribute to the protection the cells against hazardous agents.

 In this study we evaluated the impact of SFN on MRP expression and activity. The study was carried out in human intestinal Caco-2 cells. The dose and time–dependent changes in MRP activity and expression after incubation witch SFN has been studied. The expression of MRP isoform MRP1 was determined by quantitative real-time PCR (QRT-PCR). The total MRP activity was estimated by Calcein-AM Assay and visualized by confocal microscopy.

Our results have shown that SFN stronger affects the activity of MRP than its expression in Caco-2 cells.

 

 

 

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Submitted: 2012-03-26 13:51
Revised:   2014-04-28 19:16