In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

Background: Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Methods: Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. Results: In the cell death pathway, 1O2 generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15 min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-κB P65, and the enhancement of DNA fragmentation, and histone acetylation. Conclusion: ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma. © 2009 Elsevier B.V.