Antitumor Effect of Drugs Interfering with Mitochondrial Biogenesis

Abstract

Most of the rapidly growing tumors have a high capacity of aerobic glycolysis. Warburg’s hypothesis explaining this phenomenon by an impaired respiratory capacity of tumor cells attracted much attention in the past. The attempts to define the supposed defect(s) in oxidative metabolism of cancer cells were unsuccessful. Tumor mitochondria differ often very significantly from the organelles of the tissue of origin [review in 1]. These differences probably do not account for the altered, relative contributions of oxidative phosphorylation and glycolysis to the total cellular energy production in rapidly growing tumors. More relevant to the altered pattern of the tumor energy metabolism seems to be the diminished content of mitochondria in tumor cells, especially in the cells of rapidly growing tumors [review in 1]. In spite of their low content the organelles are indispensable to tumor energetics; even in the highly glycolyzing tumors oxidative phosphorylation covers no less than 50% of the energy demands of the cells [2]. Lower capacity of oxidative phosphorylation accompanying the reduced content of mitochondria in tumor cells has been employed in developing a new approach to cancer chemotherapy by using drugs interfering with the formation of functional mitochondria [3–5]. This communication deals with the mechanism by which inhibitors of mitochondrial biogenesis exert their antitumor effect.