Apoptosis in tumor cells subjected to the combined action of hyperthermia and irradiation: a study of the molecular mechanisms and targets

In the present work we investigated the molecular nature of the radiosensitizing action of hyperthermia on various cancer cells. Tumor cell lines derived from human carcinomas (HeLa, MCF-7), fibrosarcoma (HT 1080) and T-lymphoma (Jurkat) were here explored. The cell cultures were exposed to hyperthermic conditions (42-44 оС) and/or irradiated with g-photons (2-6 Gy); then such parameters were assessed as the intensity and type of cell death, clonogenicity, amounts of DNA double strand breaks and their repair dynamics, localization of heat shock proteins etc. We showed that (1) the hyperthermia-induced enhancement of post-radiation cell death is mainly due to stimulation of caspase-dependent apoptosis, (2) triggering of such apoptotic mechanism appears to result in a default of the cellular response to radiation damage to genome, (3) expression and distribution of heat shock proteins HSP90, HSP70 and HSP27 can be the important determinants defining the further fate (survival or “suicide”) of the malignant cell experienced hyperthermia and radiation exposure. It is here discussed that such factors as the heat stress response, level of aggregated cellular protein and functional activities of HSPs can substantially influence on the effectiveness of radiosensitization of tumors by heating. New approaches and targets are considered for the enhancement of radiosensitizing action of hyperthermia on cancer cells.