Mitochondrial electron transport chain blockers enhance 2-deoxy-D-glucose induced oxidative stress and cell killing in human colon carcinoma cells

Increasing evidence suggests that cancer cells (relative to normal cells) have altered mitochondrialelectron transport chains (ETC) that are more likely to form reactive oxygen species (ROS; i.e. O2•-and H2O2) resulting in a condition of chronic metabolic oxidative stress, that maybe compensated forby increasing glucose and hydroperoxide metabolism. In the current study, the ability of an inhibitor ofglucose metabolism, 2-deoxy-D-glucose (2DG), combined with mitochondrial electron transport chainblockers (ETCBs) to enhance oxidative stress and cytotoxicity was determined in human coloncancer cells. Treatment of HT29 and HCT116 cancer cells with Antimycin A (Ant A) or rotenone (Rot)increased carboxy-dichlorodihydrofluorescein diacetate (H2DCFDA) and dihydroethidine (DHE)oxidation, caused the accumulation of glutathione disulfide and enhanced 2DG-induced cell killing. Incontrast, Rot did not enhance the toxicity of 2DG in normal human fibroblasts supporting thehypotheses that cancer cells are more susceptib...