Induction of oxidative stress by hyperthermia and enhancement of hyperthermia-induced apoptosis by oxidative stress modification

Hyperthermia (HT) is considered to be a possible treatment modality for various cancers, and its pleiotropic effects support its combined use with radiotherapy and/or chemotherapy. However, clinical results by HT alone have not always been satisfactory. In mammalian cells, HT elicits a wide spectrum of alterations in cellular morphology, biochemistry and function. One of these HT-induced alterations, oxidative stress, has been attributed to the increased production of reactive oxygen spaces (ROS), and is known to play an important role as an intracellular mediator of HT-induced cell death, including apoptosis. Indeed, it has been well established that increases in intracellular oxidative stress significantly enhance HT-induced apoptosis. Attention has therefore been focused on the development of heat sensitizers to modulate the intracellular ROS. Interestingly, the modification of oxidative stress via addition of ROS-generating compounds significantly enhanced the apoptosis elicited by HT. In this chapter, we describe the induction of oxidative stress by HT and enhancement of HT-induced apoptosis by oxidative stress modification, and we discuss the possible mechanisms underlying this enhancement.