Gossypol, a hyperthermic sensitizer of HeLa cells.

Gossypol, a polyphenolic aldehyde extracted from cotton plants, is a potent antifertility agent in humans. Since we have previously reported that several male antifertility agents including 5-thio-D-glucose and lonidamine demonstrate hyperthermic sensitizing effects in HeLa cells, we wished to determine whether gossypol also exhibits the hyperthermic sensitization. Gossypol was not cytotoxic up to 4 h at 37 degrees C (10 micrograms/ml). When HeLa cells were exposed to gossypol at 41 degrees and 42 degrees C, significant potentiation of hyperthermia induced cytotoxicity was observed. The magnitude of the potentiation was dependent on the drug concentration, pH of the culture medium, glucose concentration, temperature, and duration of treatment. The hyperthermic sensitizing effect of gossypol was increased by an acidic pH and glucose deprivation. These data suggest that the sensitizing effect of the drug may be mediated through the lowering of cellular energy level by the inhibition of both glycolysis and oxidative phosphorylation.