Reversal of Intrinsic Resistance to Adriamycin in Normal Cells by Verapamil

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Abstract
Intracellular accumulation of adriamycin (ADM) was found to be increased in human breast carcinoma cell line (MCF-7) and cardiac-muscle cells as compared to an epithelial cell line derived from normal monkey kidney (CV-1) and non-muscle cells (fibroblasts) derived from the heart. This increase correlates with greater sensitivity of the carcinoma cell line to ADM. In CV-1, efflux of ADM contributes to low drug accumulation which correlates with the intrinsic drug resistance of the cells. Blockage of ADM efflux in this resistant cell line and subsequent increases in intracellular accumulation and sensitivity can be achieved by co-treatment with verapamil. ADM accumulation and sensitivity in MCF-7 however cannot be significantly increased by verapamil. These data demonstrate selectively for ADM in human breast carcinoma cell line, MCF-7 and cardiac-muscle cells in vitro. The reversal by verapamil of the normal cells' natural resistance, may have importance in the clinical use of verapamil as a resistance modulating agent.