Photodynamic Therapy Using Indolines-Fused-Triazoles Induces Mitochondrial Apoptosis in Human Non-Melanoma BCC Cells

Anticancer Res. 2017 Oct;37(10):5499-5505. doi: 10.21873/anticanres.11980.

Abstract

Background/aim: Cancer is one of the most dreadful diseases in humans and among them non-melanoma skin cancer (NMSC) is an increasing problem in the world, that occurs more frequently in people with fair skin. Photodynamic therapy (PDT), a non-invasive treatment is widely used for the prevention and treatment of BCC cells. We previously reported an efficient synthesis of novel indolines-fused-triazoles and studied their photophysical studies. This study delineated the signaling pathways involved in the PDT effect of triazoles on BCC cells under UVA irradiation.

Materials and methods: Cell survival was evaluated by the MTT assay. The uptake of 1j in BCC cells was determined by using its fluorescence properties. Intracellular ROS and mitochondrial membrane potential (ΔΨmt) were measured using DCFH-DA probe and DiOC6 dye, respectively. Cytochrome c release was determined using immunofluorescent staining.

Results: Our data disclosed that treatment of BCC cells with 1j-UVA resulted in increased ROS generation, loss of mmp (ΔΨmt), decreased levels of Bcl-2 and Bcl-xL, increased levels of Bax and Bad, cytochrome c release, and caspase-3/PARP degradation to identify apoptotic cell death.

Conclusion: The present study suggest that 1j-PDT may serve as a potential ancillary modality for the treatment of NMSC.

Keywords: Indolines-fused-triazoles; UV-light; apoptosis; mitochondria; non-melanoma; photodynamic therapy.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma, Basal Cell / drug therapy*
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Indoles / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Oxidative Stress / drug effects
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Time Factors
  • Triazoles / pharmacology*

Substances

  • Apoptosis Regulatory Proteins
  • Indoles
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Triazoles
  • indoline