Phospholipid hydroperoxide glutathione peroxidase protects against singletoxygen-induced cell damage of photodynamic therapy

Phospholipid hydroperoxide glutathione peroxidase (PhGPx) is an important e nzyme in the removal of lipid hydroperoxides (LOOHs) from cell membranes. C ancer treatments such as photodynamic therapy (PDT) induce lipid peroxidati on in cells as a detrimental action. The photosensitizers used produce reac tive oxygen species such as singlet oxygen (O-1(2)). Because singlet oxygen introduces lipid hydroperoxides into cell membranes, we hypothesized that PhGPx would provide protection against the oxidative stress of singlet oxyg en and therefore could interfere with cancer treatment. To test this hypoth esis, human breast cancer cells (MCF-7) were stably transfected with PhGPx cDNA. Four clones with varying levels of PhGPx activity were isolated. The activities of other cellular antioxidant enzymes were not influenced by the overexpression of PhGPx. Cellular PhGPx activity had a remarkable inverse linear correlation to the removal of lipid hydroperoxides in living cells ( r = -0.85), and correlated positively with cell survival after singlet oxyg en exposure (r = 0.94). These data demonstrate that PhGPx provides signific ant protection against singlet oxygen generated lipid peroxidation via remo val of LOOH and suggest that LOOHs are major mediators in this cell injury process. Thus, PhGPx activity could contribute to the resistance of tumor c ells to PDT. (C) 2001 Elsevier Science Inc.