Enhancement of Hyperthermia-induced Apoptosis by Modification of Intracellular Oxidative Stress

Hyperthermia (HT) for cancer therapy combined with radiation and anticancer agents has been clinically used and has shown good results to a certain extent. However, clinical results by HT alone have not always been satisfactory. Although HT induces cancer cell death by apoptosis, the degree of apoptosis and its pathway varies in different cancer cell types. Therefore, attention has been focused on the search for substances to sensitize cancer cells to HT-treatment without affecting normal cells. Since it is known that HT can induce intracellular oxidative stress in cells and tissues because of increased production of reactive oxygen species (ROS) within cells, modification of intracellular oxidative stress could play a critical role in both sensitization and protection of apoptosis induced by HT. In this review, some evidence on enhancement of HT-induced apoptosis by increase of intracellular oxidative stress, such as the use of temperature-dependent free radical generators, an intracellular hydrogen peroxide (H2O2) generator and an intracellular oxidative stress specific nitric oxide (NO・) donor, will be shown and the mechanisms of the enhancement will be discussed.