Hyperthermia-induced biochemical and ultrastructural modifications in cultured cells

Hyperthermia has been used in cancer treatment for many years. The effect of hyperthermia is particularly beneficial against tumours when used together with chemotherapy or radiotherapy. There is considerable interest for the use of clinical hyperthermia combined with anticancer agents with the aim of enhancing the cytotoxicity of these agents in localised target regions of a tumour. Of primary interest are thermosensitizers, compound that become much more toxic at elevated temperatures. Mle showed that the thermosensitizing activity of aldehyde(s) produced in the bovine serum amine oxidase catalysed oxidation of polyamines has potential value for improving the therapeutic effects of hyperthermia and could be used as a new anticancer strategy. Polyamine concentrations are high in growing tissues such as tumours and has been considered as heat sensitizers. Moreover, since the cell membranes and the cytoskeletal components are important sites of the mechanism of action of hyperthermia, agents that cause modification of these cellular structures may affect the cell response to heat. The pretreatment of tumour cells with multilamellar liposomes, capable of fusing with the plasma membrane, induced a potentiation of the hyperthermic damage on cultured cells. in addition, the cytotoxic effects induced by liposome-cell interaction showed to be enhanced under mild hyperthermic conditions. Finally, the polar solvent N-methylformamide proved to prevent morphological changes and cell detachment induced by the heat treatment. This antagonistic action could be due to the combined effects of the polar solvent and hyperthermia on the cytoskeletal organization.