Novel sulfonamide porphyrin TBPoS-2OH used in photodynamic therapy for malignant melanoma

Biomed Pharmacother. 2021 Jan:133:111042. doi: 10.1016/j.biopha.2020.111042. Epub 2020 Dec 8.

Abstract

The application of photodynamic therapy (PDT) for the treatment of skin diseases has been receiving much attention. Here, we examined the anti-tumor effect of a novel porphyrin-based photosensitizer TBPoS-2OH in the malignant melanoma A375 and B16 cells. TBPoS-2OH has obvious cell photo-cytotoxicity, but it has low cell dark-cytotoxicity. Further research showed that TBPoS-2OH is enriched in lysosomes after being taken up by cells. Subsequently, the apoptotic rates were significantly increased in TBPoS-2OH-treated A375 and B16 cells. The specific mechanism may be that after receiving light stimulation, TBPoS-2OH could effectively increase the level of intracellular reactive oxygen species (ROS), thereby activating mitochondrial apoptosis pathway-related proteins in A375 and B16 cells. We found an increase in the content of cytochrome C in the cytoplasm, and the levels of related proteins, such as cleaved caspase-3, cleaved caspase-9, and cleaved PARP1, were significantly increased in TBPoS-2OH-treated cells. These results indicated that the new compound TBPoS-2OH could be developed and become an alternative drug for the treatment of melanoma. Some reference ideas for the development of new photosensitizers are also provided.

Keywords: Melanoma; Mitochondria-mediated apoptosis; Photodynamic therapy; Porphycene; ROS; Tumor.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Sulfonamides / pharmacology*

Substances

  • Apoptosis Regulatory Proteins
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Sulfonamides