Nitroxide TEMPOL impairs mitochondrial function and induces apoptosis in HL60 cells

The piperidine nitroxide TEMPOL induces apoptosis in a number of tumor cell lines through free radical-dependent mechanisms. As mitochondria play a ma jor role in apoptosis as both source and target for free radicals, the pres ent study focuses on mitochondrial effects of TEMPOL in a human promyelocyt ic leukemic cell line (HL-60). On 24-h exposure to TEMPOL, the following al terations were observed: 1) decrease in both the intracellular and mitochon drial glutathione pools; 2) impairment of oxidative phosphorylation; and 3) decrease in mitochondrial membrane potential. In addition, TEMPOL was foun d to specifically target complex I of the respiratory chain, with minor eff ects on complexes II and IV, suggesting that mitochondrial effects might pl ay a role in TEMPOL-induced oxidative stress and apoptosis, and that TEMPOL might sensitize tumor eel Is to the pro-apoptotic effects of cytotoxic age nts. J. Cell. Biochem. 82: 271-276, 2001. (C) 2001 Wiley-Liss, Inc.