Blue light induced reactive oxygen species from flavin mononucleotide and flavin adenine dinucleotide on lethality of HeLa cells

J Photochem Photobiol B. 2017 Aug:173:325-332. doi: 10.1016/j.jphotobiol.2017.06.014. Epub 2017 Jun 13.

Abstract

Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm). Under blue light irradiation at 3.744J/cm2 (=0.52mW/cm2 irradiated for 2h), the minimal lethal dose is 3.125μM and the median lethal doses (LD50) for FMN and FAD are 6.5μM and 7.2μM, respectively. Individual exposure to visible blue light irradiation or riboflavin photosensitizers does not produce cytotoxicity and no side effects are observed in this study. The western blotting results also show that an intrinsic apoptosis pathway is activated by the ROS during photolysis of riboflavin analogues. Blue light triggers the cytotoxicity of riboflavins on HeLa cells in vitro. Based on these results, this is a feasible and efficient of PDT with an intrinsic photosensitizer for cancer research.

Keywords: Apoptosis; Hypoxia; Light emitting diode; Photodynamic therapy; Riboflavin photosensitizer.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • Flavin Mononucleotide / metabolism
  • Flavin Mononucleotide / pharmacology*
  • Flavin-Adenine Dinucleotide / metabolism
  • Flavin-Adenine Dinucleotide / pharmacology*
  • HeLa Cells
  • Humans
  • Light*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Photolysis / drug effects
  • Photolysis / radiation effects
  • Photosensitizing Agents / metabolism
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism*

Substances

  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Flavin-Adenine Dinucleotide
  • Flavin Mononucleotide