Nitroxide TEMPOL impairs mitochondrial function and induces apoptosis in HL60 cells

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Abstract
The piperidine nitroxide TEMPOL induces apoptosis in a number of tumor cell lines through free radical‐dependent mechanisms. As mitochondria play a major role in apoptosis as both source and target for free radicals, the present study focuses on mitochondrial effects of TEMPOL in a human promyelocytic leukemic cell line (HL‐60). On 24‐h exposure to TEMPOL, the following alterations were observed: 1) decrease in both the intracellular and mitochondrial glutathione pools; 2) impairment of oxidative phosphorylation; and 3) decrease in mitochondrial membrane potential. In addition, TEMPOL was found to specifically target complex I of the respiratory chain, with minor effects on complexes II and IV, suggesting that mitochondrial effects might play a role in TEMPOL‐induced oxidative stress and apoptosis, and that TEMPOL might sensitize tumor cells to the pro‐apoptotic effects of cytotoxic agents. J. Cell. Biochem. 82: 271–276, 2001.