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/DoxR). MCF7/DoxR cells were resistant to hyperthermia and Rh123. Hyperthermic potentiation of Rh123 cytotoxicity was present in MCF7/WT but not in MCF7/DoxR 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/DoxR 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.
National Neurologic Institute C. Besta, Milan, Italy.
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Gritti
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Colombo
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Dasdia
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Melloni
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Marchesini
D001693:Biological Transport, Active; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D020112:Rhodamine 123; D012235:Rhodamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D005456:Fluorescent Dyes; D012235:Rhodamines; D020112:Rhodamine 123; D004317:Doxorubicin