Elucidation of singlet oxygen-induced cell death

Although singlet oxygen plays a pivotal role in ultraviolet-induced skin photoaging and cellular damage during photodynamic therapy, the mechanism associated with its cytotoxicity is not fully understood. The effects of endoperoxides that generate defined amounts of singlet oxygen were examined in this study. An endoperoxide that appears to be membrane permeable exerted severe cytotoxicity, suggesting that the target molecule is located deep inside the cells. Even though singlet oxygen triggered the release of cytochrome c from mitochondria and cell death, it induced much less DNA ladder formation and nuclear fragmentation than etoposide. This was found to be due to the suppression of caspase activation by singlet oxygen. Thus, singlet oxygen causes the inactivation of caspases, most probably by affecting the cysteine residue in the catalytic center, and consequently aborts apoptosis.