Effect of hyperthermia on rhodamine 123 cytotoxicity in doxorubicin-sensitive and doxorubicin-resistant human breast carcinoma cell lines in vitro

Rhodamine 123 (Rh123) cytotoxicity and intracellular accumulation were studied in normothermic and hyperthermic conditions in a human breast carcinoma cell line (MCF7/WT) and its doxorubicin-resistant subline (MCF7/Dox(R)). MCF7/Dox(R) cells were resistant to hyperthermia and Rh123. Hyperthermic potentiation of Rh123 cytotoxicity was present in MCF7/WT but not in MCF7/Dox(R) cells. Results suggest that the effect observed in MCF7/WT cells is related to a heat-induced increased accumulation of Rh123 and not to a heat-induced activation of the drug. A low basal uptake and a fast release of Rh123 could explain the resistance of MCF7/Dox(R) to the drug. Resistance to Rh123 and lack of a heat-induced increased uptake account for the lack of hyperthermic enhancement of Rh123 cytotoxicity in the resistant cells.