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.