Dano ao DNA induzido por fotoclivagem e análise citotóxica de uma porfirina meso-tetra-rutenada sob irradiação por luz visível

Abstract

Photodynamic Therapy (PDT) combined with the use of molecules containing the porphyrin ring associated with ruthenium transition metal has become an alternative method to the traditional treatment of melanoma. Here, we demonstrate DNA damage analyses, photocleavage properties and cytotoxicity of a free-based meso-terta-ruthenated porphyrin (H2RuTPyP). Cytotoxic and genotoxic potential of H2RuTPyP was investigated by colorimetric assay and by plasmid DNA photocleavage analysis followed by incubation with specific DNA repair enzymes, respectively. H2RuTPyP porphyrin efficiently induced DNA damage at the lowest concentration of 5.0 μM, resulting in its complete degradation at 15 μM. The presence of different scavengers for reactive oxygen species during exposure to visible light did not decrease the formation of DNA breaks, suggesting a hydrolytic mechanism for the breakdown of this molecule. In addition, the compound H2RuTPyP exhibited a higher cytotoxicity towards melanoma cell line compared to keratinocytes. Therefore, H2RuTPyP compound demonstrated to be a very promising effective photosensitizer, representing an alternative for the development of new treatments for melanoma by PDT.