Artesunate restrains the malignant progression of human cutaneous squamous cell carcinoma cells via the suppression of the PI3K/AKT pathway

Tissue Cell. 2022 Jun:76:101789. doi: 10.1016/j.tice.2022.101789. Epub 2022 Mar 19.

Abstract

Purpose: Artesunate (ART) is recognized for its anticancer activity, but a few studies concentrate on its anti-skin cancer effect. This study emphazied this aspect and preliminarily discussed the impact and mechanism of ART on cutaneous squamous cell carcinoma (CSCC).

Methods: The viability of HaCaT and CSCC cells treated with ART (0, 30, 60, 90, 120, 150, 180, or 210 μmol/L) for 48 h were assessed utilizing cell counting kit-8. Next, the migration, invasion, proliferation, apoptosis, and cell cycle of CSCC cells treated with ART were evaluated by dint of cell function experiments. Then, cell cycle-, apoptosis-, and phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related markers were examined via western blot or quantitative real-time PCR. Moreover, the influences of ART and PI3K/AKT agonist IGF-I on CSCC cell biological behaviors were gauged again.

Results: The suppressive role of ART (30, 60, 90, 120, 150, 180, or 210 μmol/L) was stronger in viability of CSCC cells than in viability of HaCaT cells. ART evidently attenuated the migration, invasion and proliferation, lessened cell numbers at G2/M phase and triggered apoptosis of CSCC cells. At the molecular level, ART regulated cell cycle-, apoptosis-, and PI3K/AKT pathway-related markers in CSCC cells. Moreover, the suppression of ART on CSCC cell malignant phenotypes was reversed by PI3K/AKT agonist IGF-I.

Conclusion: ART restrains the malignant progression of CSCC, which may be intensely related to the PI3K/AKT pathway repression.

Keywords: Apoptosis; Artesunate; Cell cycle; Cutaneous squamous cell carcinoma; PI3K/AKT pathway.

MeSH terms

  • Apoptosis
  • Artesunate / pharmacology
  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Humans
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Skin Neoplasms* / drug therapy

Substances

  • Artesunate
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt