5-ALA-PDT induced ferroptosis in keloid fibroblasts via ROS, accompanied by downregulation of xCT, GPX4

Photodiagnosis Photodyn Ther. 2023 Jun:42:103612. doi: 10.1016/j.pdpdt.2023.103612. Epub 2023 May 21.

Abstract

Keloids display many cancerous properties, including uncontrolled and invasive growth, high rates of recurrence as well as similar bioenergetics. 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) is an effective treatment that performs cytotoxic effects by producing reactive oxygen species (ROS), which is linked to lipid peroxidation and ferroptosis. Herein, we explored underlying mechanisms of 5-ALA-PDT against keloids. We identified that 5-ALA-PDT led to elevated levels of ROS and lipid peroxidation in keloid fibroblasts, accompanied by downregulation of xCT and GPX4, which are associated with anti-oxidation effects and ferroptosis inhibition. These results may indicate that 5-ALA-PDT treatment increases ROS while inhibiting xCT and GPX4, thus promoting lipid peroxidation to induce ferroptosis in keloid fibroblasts.

Keywords: Ferroptosis; Fibroblast; Keloids; PDT.

MeSH terms

  • Aminolevulinic Acid / pharmacology
  • Aminolevulinic Acid / therapeutic use
  • Down-Regulation
  • Ferroptosis*
  • Fibroblasts
  • Humans
  • Keloid* / drug therapy
  • Photochemotherapy* / methods
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Reactive Oxygen Species / metabolism

Substances

  • Aminolevulinic Acid
  • Reactive Oxygen Species
  • Photosensitizing Agents