Survival response of a human glioma cell line to hyperthermia associated with rhein.

The effect of association of hyperthermia with the anti-inflammatory drug rhein (RH), 4,5-dihydroxyanthraquinone-2-carboxylic acid, on the clonogenic activity of human glioma cells has been examined. RH inhibits neoplastic growth mainly through an ATP depletion, but thermal cell killing is not mediated by the drug-induced changes in the energy status of the cell. The analysis of the interaction between RH and hyperthermia, performed with the isobolar method, demonstrates an additivity of the response so that the effectiveness of the combined treatment is the result of two independent effects. Although the effect of this combination is purely additive, RH allows us to achieve a pre-established cell killing with exposure times at 42 degrees C, which is generally accepted to be clinically achievable. RH might, therefore, be employed to reduce the side effects of hyperthermia without impairing its therapeutic effectiveness.