Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells

Hyperthermia treatments (43 degrees C, 1 h) were performed on exponentially growing MCF-7 breast adenocarcinoma cells at the beginning, middle, or end of 24 h incubations of the cells in vitro with Taxol (paclitaxel). When th e cells were heated at the beginning or middle of the Taxol incubation, the hyperthermia treatment protected against the toxic effect of each of the T axol concentrations examined (5, 10 and 100 nM). Consistent with earlier st udies, Taxol treatment at 37 degrees C resulted in an accumulation of great er than 94% of the cells in G2/M at 24 h. Heating the cells at the middle o r end of the Taxol treatment resulted in a similar accumulation. However, h eat treatment during the first hour of Taxol exposure resulted in a signifi cantly smaller percentage of cells (similar to 50%) in G2/M. HPLC analysis showed that at 37 degrees C, Taxol uptake into MCF-7 cells approached maxim um within 0.25 h and increased only slightly more over the next 11.75 h. Th e parental Taxol level was markedly lower by 24 h. In contrast, 1 h hyperth ermia treatments at the beginning or middle of the Taxol incubation resulte d in higher Taxol concentrations at 12 and 24 h, and higher intracellular c oncentrations overall than at 37 degrees C. These results indicate that hyp erthermia inhibits Taxol related cell cycle effects and cytotoxicity, in sp ite of causing higher concentrations of Taxol to be present in heated cells .