Uncoupling protein 2 and mitochondrial bioenergetics in drug-sensitive and drug-resistant leukemic cells.

Abstract

The overall objective of this research was to characterize the differences in the metabolic control of oxidative phosphorylation in drug sensitive and drug resistant leukemic cells. Anti-cancer agents may function to promote tumor cell death in a number of ways, however acquired or inherent drug resistance is a major problem in successful cancer treatment. The role of mitochondria in apoptosis has received a great deal of attention from a variety of biochemical perspectives in the past few years. Based on evidence that mitochondrial metabolism is altered during apoptotic processes, this research built on the hypothesis that an alteration in mitochondrial energy metabolism which decreases the production of reactive oxygen species plays a significant role in the protection of tumor cells from cytotoxic therapies. Two pairs of sensitive and resistant leukemic cell lines were studied: the mouse L1210 cell line and its drug resistant L1210/DDP subline, as well as the human HL60 cell line and the HL60/MDR resistant cell line. (Abstract shortened by UMI.)