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19.09.

2022, 19:52 Sulforaphane and erucin increase MRP1 and MRP2 in human carcinoma cell lines - ScienceDirect

The Journal of Nutritional Biochemistry


Volume 19, Issue 4, April 2008, Pages 246-254

Research article

Sulforaphane and erucin increase MRP1 and MRP2 in human


carcinoma cell lines
Kristin E. Harris, Elizabeth H. Jeffery

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https://doi.org/10.1016/j.jnutbio.2007.02.014 Get rights and content

Abstract
Multidrug resistance (MDR) transporters have been termed the Phase III detoxification system because
they not only export endogenous metabolites but provide protection from xenobiotic insult by actively
secreting foreign compounds and their metabolites from tissues. However, MDR overexpression in tumors
can lead to drug resistance, a major obstacle in the treatment of many cancers, including lung cancer.
Isothiocyanates from cruciferous vegetables, such as sulforaphane (SF) and erucin (ER), are known to
enhance the expression of Phase II detoxification enzymes. Here we evaluated the ability of SF and ER to
modulate MDR mRNA and protein expressions, as well as transporter activity. The expression of P-
glycoprotein (P-gp), multidrug resistance protein 1 (MRP1) and multidrug resistance protein 2 (MRP2) in
liver (HepG2), colon (Caco-2) and lung (A549) cancer cells treated with ER or SF was analyzed by Western
blotting. Neither SF nor ER affected P-gp expression in any of the cell lines tested. Both SF and ER
increased the protein levels of MRP1 and MRP2 in HepG2 cells and of MRP2 in Caco-2 cells in a dose-
dependent manner. In A549 lung cancer cells, SF increased MRP1 and MRP2 mRNA and protein levels; ER
caused a similar yet smaller increase in MRP1 and MRP2 mRNA. In addition, SF and ER increased MRP1-
dependent efflux of 5-carboxyfluorescein diacetate in A549 cells, although again the effect of SF was
substantially greater than that of ER. The implication of these findings is that dietary components that
modulate detoxification systems should be studied carefully before being recommended for use during
chemotherapy, as these compounds may have additional influences on the disposition of chemotherapeutic
drugs.

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Keywords
Sulforaphane; Erucin; Multidrug resistance

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