title: 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.
authors.affiliation: University of Medicine and Pharmacy, Department of Physiology, Clinicilor 1, Cluj-Napoca, Romania. Electronic address: baldeai@yahoo.com.
authors.forename: Ioana
authors.initials: I
authors.lastname: Baldea
authors.affiliation: University of Medicine and Pharmacy, Department of Physiology, Clinicilor 1, Cluj-Napoca, Romania. Electronic address: ariana_di@yahoo.com.
authors.forename: Diana Elena
authors.initials: DE
authors.lastname: Olteanu
authors.affiliation: University of Agricultural Sciences and Veterinary Medicine, Department of Pathology, Calea Manastur 3-5, 400372 Cluj-Napoca, Romania; Ross University School of Veterinary Medicine, Department of Biomedical Sciences, PO Box 334, Basseterre, Saint Kitts and Nevis. Electronic address: pompei.bolfa@usamvcluj.ro.
authors.forename: Pompei
authors.initials: P
authors.lastname: Bolfa
authors.affiliation: National Institute for Research & Development in Chemistry and Petrochemistry - ICECHIM, Nanomedicine Research Group, 202 Splaiul Independentei, Sector 6, Bucharest, Romania. Electronic address: rodicaion2000@yahoo.co.uk.
authors.forename: Rodica Mariana
authors.initials: RM
authors.lastname: Ion
authors.affiliation: University of Medicine and Pharmacy, Department of Physiology, Clinicilor 1, Cluj-Napoca, Romania. Electronic address: nicoleta_decea@yahoo.com.
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Decea
authors.affiliation: University of Agricultural Sciences and Veterinary Medicine, Department of Biochemistry, Calea Manastur 3-5, 400372 Cluj-Napoca, Romania. Electronic address: mihai.cenariu@usamvcluj.ro.
authors.forename: Mihai
authors.initials: M
authors.lastname: Cenariu
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babeş-Bolyai University, Clinicilor Street 5-7, 400006 Cluj-Napoca, Romania. Electronic address: manuela.banciu@ubbcluj.ro.
authors.forename: Manuela
authors.initials: M
authors.lastname: Banciu
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babeş-Bolyai University, Clinicilor Street 5-7, 400006 Cluj-Napoca, Romania. Electronic address: alina.sesarman@hasdeu.ubbcluj.ro.
authors.forename: Alina Viorica
authors.initials: AV
authors.lastname: Sesarman
authors.affiliation: University of Medicine and Pharmacy, Department of Physiology, Clinicilor 1, Cluj-Napoca, Romania. Electronic address: adrianafilip33@yahoo.com.
authors.forename: Adriana Gabriela
authors.initials: AG
authors.lastname: Filip
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C000615594:5-(4-hydroxyphenyl)-10,15,20-tris(4-methoxyphenyl)porphyrin; D000970:Antineoplastic Agents; D000975:Antioxidants; D016328:NF-kappa B; D017319:Photosensitizing Agents; D011166:Porphyrins; D014409:Tumor Necrosis Factor-alpha; C000614533:meso-5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin; D013482:Superoxide Dismutase
keywords: Apoptosis; Melanogenesis; Melanoma; Meso-5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin; Meso-5-(4-hydroxyphenyl)-10,15,20-tris (4-methoxyphenyl) porphyrin; Oxidative stress; Photodynamic therapy