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

Oncol Rep. 2013 Mar;29(3):1196-200. doi: 10.3892/or.2012.2190. Epub 2012 Dec 14.


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.

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Beclin-1
  • Caspases / metabolism
  • Cathepsin B / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Melanins / metabolism*
  • Melanoma, Experimental
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Photochemotherapy
  • Photosensitizing Agents / pharmacology*
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / metabolism


  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Becn1 protein, mouse
  • Map1lc3b protein, mouse
  • Melanins
  • Microtubule-Associated Proteins
  • PUMA protein, mouse
  • Photosensitizing Agents
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Aminolevulinic Acid
  • Caspases
  • Cathepsin B
  • Ctsb protein, mouse