The third-generation retinoid adapalene triggered DNA damage to induce S-phase arrest in HaCat cells

Fundam Clin Pharmacol. 2020 Jun;34(3):380-388. doi: 10.1111/fcp.12527. Epub 2019 Dec 23.

Abstract

Epidermal proliferative diseases consisted of a series of common skin diseases, most of which were recurrent chronic skin diseases, and had greatly negative influence on the life quality of patient. Retinoids exhibited vital roles in the treatment of many skin diseases. Our recent study demonstrated that adapalene significantly inhibited the growth of HaCat cells, and the inhibitory activity was stronger than other retinoids, such as all-trans-retinoic acid, acitretin, isotretinoin, tazarotene, and bexarotene. Further study showed that adapalene suppressed the colony formation of HaCat cells, and it dramatically triggered S-phase arrest and apoptosis, rather than G1 phase arrest which was reported in other retinoids in several studies. Additionally, adapalene treatment greatly upregulated the protein expression of DNA damage marker γ-H2AX, which was in accord with the results of the elongation of tail moment by comet electrophoresis analysis. Moreover, DNA damage was triggered and DNA repair was suppressed synchronously with adapalene treatment, which accounted for the mechanism of S-phase arrest induced by adapalene. In summary, our recent work demonstrated that adapalene showed strong anti-proliferation activity in HaCat cells and could be an alternative agent for the epidermal proliferative disease.

Keywords: DNA damage; S-phase arrest; adapalene; apoptosis; epidermal proliferative diseases; γ-H2AX.

MeSH terms

  • Adapalene / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects
  • DNA Damage / drug effects*
  • DNA Repair / drug effects
  • G1 Phase / drug effects
  • HaCaT Cells
  • Humans
  • Nicotinic Acids / pharmacology
  • Retinoids / pharmacology*
  • S Phase / drug effects*
  • Up-Regulation / drug effects

Substances

  • Nicotinic Acids
  • Retinoids
  • Adapalene
  • tazarotene