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

Abstract

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