Pluronic block copolymers have been shown to sensitize
cancer cells resulting in an increased activity of
antineoplastic agents. In the current study we examined a new application of
Pluronic bioactivity in potentiating
hyperthermia-induced cancer cell injury. DHD/K12/TRb rat
adenocarcinoma cells were exposed to low-grade
hyperthermia at 43 degrees C with or without
Pluronic P85 or
Pluronic L61. A range of
Pluronic doses, pre-exposure and heat exposure durations were investigated, and the test conditions were optimized. Treatment efficacy was assessed by measurement of intracellular
ATP and mitochondrial
dehydrogenase activity. Both P85 and L61 in synergy with heat reduced cell viability appreciably compared to either heat or
Pluronic alone. Under optimal conditions, P85 (10 mg/ml, 240 mins) combined with 15 mins heat reduced intracellular
ATP to 60.1 +/- 3.5% of control, while heat alone and P85 without heat caused a negligible decrease in
ATP of 1.2% and 3.8%, respectively. Similarly, cells receiving 120 mins pre-exposure of L61 (0.3 mg/ml) showed reduction in intracellular
ATP to 14.1 +/- 2.1% of control. Again, heat or L61 pre-exposure alone caused a minor decrease in levels of intracellular
ATP (1.5% and 4.4%, respectively). Comparable results were observed when viability was assessed by mitochondrial
enzyme activity. Survival studies confirmed that the loss of viability translates to a long-term reduction in proliferative activity, particularly for L61 treated cells. Based on these results, we conclude that
Pluronic is effective in improving hyperthermic
cancer treatment in vitro by potentiating heat-induced cytotoxicity in a concentration and time dependent manner.