Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Sparsa,Agnès; Bellaton,Solenn; Naves,Thomas; Jauberteau,Marie-Odile; Bonnetblanc,Jean-Marie; Sol,Vincent; Verdier,Mireille; Ratinaud,Marie-Hélène

doi:10.3892/or.2012.2190

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Authors:
- Agnès Sparsa
- Solenn Bellaton
- Thomas Naves
- Marie-Odile Jauberteau
- Jean-Marie Bonnetblanc
- Vincent Sol
- Mireille Verdier
- Marie-Hélène Ratinaud
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Affiliations: EA 3842 Cellular Homeostasis and Pathology, Faculty of Medicine, University of Limoges, 87025 Limoges Cedex, France, Department of Dermatology, University Hospital Dupuytren, 87042 Limoges Cedex, France, Chemistry Laboratory of Natural Substances, Faculty of Sciences, 87060 Limoges Cedex, France
Published online on: December 14, 2012 https://doi.org/10.3892/or.2012.2190
Pages: 1196-1200

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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.

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