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[Cancer Research 60, 47-50, January 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Fumitremorgin C Reverses Multidrug Resistance in Cells Transfected with the Breast Cancer Resistance Protein1

Sridhar K. Rabindran2, Douglas D. Ross, L. Austin Doyle, Weidong Yang and Lee M. Greenberger

Oncology & Immunoinflammatory Research, Wyeth-Ayerst Research, Pearl River, NY 10965 [S. K. R., L. M. G.]; Greenebaum Cancer Center of the University of Maryland, Baltimore, Maryland 21201 [D. D. R., L. A. D., W. Y.]; Department of Medicine, Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201 [D. D. R., L. A. D.]; and Baltimore Veterans Medical Center, Department of Veterans Affairs, Baltimore, Maryland 21201 [D. D. R.]

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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