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

SK Rabindran, DD Ross, LA Doyle, W Yang… - Cancer research, 2000 - AACR
SK Rabindran, DD Ross, LA Doyle, W Yang, LM Greenberger
Cancer research, 2000AACR
Fumitremorgin C (FTC) is a potent and specific chemosensitizing agent in cell lines selected
for resistance to mitoxantrone that do not overexpress P-glycoprotein or multidrug resistance
protein. The gene encoding a novel transporter, the breast cancer resistance protein
(BCRP), was recently found to 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
may contain multiple alterations contributing to the multidrug resistance phenotype, we …
Abstract
Fumitremorgin C (FTC) is a potent and specific chemosensitizing agent in cell lines selected for resistance to mitoxantrone that do not overexpress P-glycoprotein or multidrug resistance protein. The gene encoding a novel transporter, the breast cancer resistance protein(BCRP), was recently found to 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 may contain multiple alterations contributing to the multidrug resistance phenotype, we examined the effect of FTC on MCF-7 cells transfected with the BCRP gene. We report that FTC almost completely reverses resistance mediated by BCRP in vitro and is a pharmacological probe for the expression and molecular action of this transporter.
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