title: Photodynamic treatment induces cell death by apoptosis or autophagy             depending on the melanin content in two B16 melanoma cell lines.
abstract: Photodynamic therapy (PDT) is now a well-established treatment modality             for cutaneous carcinomas and is based on the administration of a light-activated             drug followed by illumination of the pathological area. The treatment of metastatic             melanoma remains a therapeutic challenge. To define the possible role of melanin             in relative phototoxicity of 5-aminolevulinic acid (5-ALA), a photosensitizer             used in PDT in vivo, we studied cell death in two variants (with or without melanin,             B16F10 and B16G4F cells, respectively) of a melanoma cell line. Concentrations             of 5-Ala up to 10 mM induced similar cytostatic effects in the B16G4F and B16F10             cells. PDT and high 5-ALA concentrations induced photocytotoxicity in both melanoma             cell lines (at 10 mM for B16F10 cells and at 5 mM for B16G4F cells). Cell death             corresponded to p53-dependent apoptotic signaling in pigmented B16F10 cells, whereas             an autophagic response leading to a caspase-independent death was detected in             non-pigmented B16G4F cells. Therefore, the PDT-induced cell death pathway appeared             to correlate with melanin synthesis capacity in melanoma cells. To reduce the             cytotoxicity of 5-ALA without irradiation, a low drug concentration could be used.             Consequently, in combination with current therapeutics, a moderate concentration             of 5-ALA and PDT may constitute a supplementary promising approach to eliminate             metastatic melanoma.
authors.affiliation: EA 3842 Cellular Homeostasis and Pathology, Faculty of Medicine,                     University of Limoges, 87025 Limoges Cedex, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Sparsa
authors.forename: Solenn
authors.initials: S
authors.lastname: Bellaton
authors.forename: Thomas
authors.initials: T
authors.lastname: Naves
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Jauberteau
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bonnetblanc
authors.forename: Vincent
authors.initials: V
authors.lastname: Sol
authors.forename: Mireille
authors.initials: M
authors.lastname: Verdier
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Ratinaud
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D020169:Caspases / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; D008543:Melanins; D008869:Microtubule-Associated Proteins; C488588:PUMA protein, mouse; D017319:Photosensitizing Agents; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000622:Aminolevulinic Acid; D020169:Caspases; D002401:Cathepsin B; C533915:Ctsb protein, mouse