Photodynamic properties of meta-tetra(hydroxyphenyl)chlorin in human tumor cells.
The photodynamic properties of a second-generation photodynamic sensitizer, meta-tetra(hydroxyphenyl)chlorin (mTHPC) were studied by dye-sensitized photoinactivation (650 nm) of HT29 human adenocarcinoma cells in culture. The photocytotoxicity of mTHPC in vitro depended on the presence of molecular oxygen. A strong inhibition of the photocytotoxicity of mTHPC was observed upon addition of sodium azide, a known singlet oxygen quencher. Photocytotoxicity was not inhibited by scavengers of superoxide anion radical, hydrogen peroxide and hydroxyl radicals. We suggest that mTHPC photosensitizes cell killing predominantly by type II, singlet oxygen-mediated photodynamic reactions. Illumination of cells preloaded with mTHPC induced peroxidation of membrane lipids. Inhibition of photoperoxidation by alpha-tocopherol (0.1 mM) present during illumination did not result in any decrease in toxicity, suggesting that reactions of lipid peroxidation play only a minor role in the overall photocytotoxic effect of mTHPC.
Melnikova
V O
VO
Unité de Recherche en Thérapie Photodynamique, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France 54511.
Bezdetnaya
L N
LN
Potapenko
A Y
AY
Guillemin
F
F
D002470:Cell Survival / Q000187:drug effects; D005292:Ferricyanides / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D015227:Lipid Peroxidation; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017382:Reactive Oxygen Species
D005292:Ferricyanides; D016166:Free Radical Scavengers; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C072269:temoporfin; C028033:potassium ferricyanide