Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein

Fumitremorgin C (FTC) is a potent and specific chemosensitizing agent in ce ll lines selected for resistance to mitoxantrone that do not overexpress P- glycoprotein or multidrug resistance protein. The gene encoding a novel tra nsporter, the breast cancer resistance protein (BCRP), was recently found t o be overexpressed in a mitoxantrone-selected human colon cell line, S1-M1- 3.2, which was used to identify FTC. Because the drug-selected cell line ma y contain multiple alterations contributing to the multidrug resistance phe notype, we examined the effect of FTC on MCF-7 cells transfected with the B CRP gene. We report that FTC almost completely reverses resistance mediated by BCRP in vitro and is a pharmacological probe for the expression and mol ecular action of this transporter.