Abstract
Rhodamine 123 (R123) cytotoxicity and intracellular accumulation were studied at elevated temperature in R123-sensitive and R123-resistant B16 mouse melanoma cell lines. Hyperthermic potentiation of R123 cytotoxicity, present in the parental R123-sensitive cell line, was not present in the R123-resistant cell line. R123-resistant melanoma cells did not develop concomitant resistance to hyperthermia. Hyperthermic potentiation of R123 cytotoxicity was restored in the resistant cells by co-treatment with verapamil. Restoration of hyperthermic potentiation of R123 by verapamil in R123-resistant cells was accompanied by increased intracellular accumulation and decreased efflux of R123. These results suggest that verapamil may be used to re-establish thermal enhancement of drug cytotoxicity when thermochemotherapeutic resistance is present.
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