Efficiency of photodynamic therapy on WM35 melanoma with synthetic porphyrins: Role of chemical structure, intracellular targeting and antioxidant defense

摘要: Photodynamic therapy (PDT) could be an adjuvant in melanoma, aggressive cancer that arises from melanocytes. Several reports showed encouraging results of the efficacy PDT melanoma on experimental models and clinical trials. Therefore, we studied two derivatives tetraphenylporphyrin (TPP): meso-5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin (THOPP) meso-5-(4-hydroxyphenyl)-10,15,20-tris (4-methoxyphenyl) (THOMPP) as photosensitizers for PDT, compared to FDA approved delta aminolevulinic acid (ALA) against a lightly pigmented, cell line, WM35, vitro. Both porphyrins were more efficient photosensitizers, ALA, without dark toxicity. The efficiency depended intracellular localization molecule structure. THOPP, most localized mainly mitochondria, while THOMPP accumulated lysosomes; both melanosomal localization. symmetric THOPP was able generate increased oxidative stress damage apoptosis. also induced low effect defense mechanisms like antioxidant enzyme SOD (superoxide dismutase), NF-kB (nuclear transcription factor kB) activation MITF (microphthalmia factor). lower asymmetric molecule, probably due diminished photoactivation, which led ROS damage, combined with higher mechanisms.