Halofuginone inhibits cell proliferation and AKT/mTORC1 signaling in uterine leiomyoma cells

Growth Factors. 2022 Nov;40(5-6):212-220. doi: 10.1080/08977194.2022.2113394. Epub 2022 Aug 24.

Abstract

The present study aimed to explore the effects of antifibrotic agent halofuginone on uterine leiomyomas (ULs) cells. The survival of the uterine smooth muscle (UtSMC) cells and UL ELT3 cells were measured. Flow cytometry was used to assess the cell cycle distribution and apoptosis. Effects of halofuginone on the state of AKT/mTOR pathway were evaluated. Xenograft animal model was applied to explore the effects of halofuginone in vivo. Halofuginone inhibited the proliferation of ELT3 cells dose-dependently without obvious influence on UtSMC cells. Halofuginone suppressed cell cycle progression and promoted apoptosis of ELT3 cells dose-dependently. Also, p-AKT/AKT and p-p70S6/p70S6 were significantly lowered after treatment with 20 nM halofuginone. Additionally, halofuginone reduced ELT3 tumor growth in xenograft tumor animal model. The present study illustrates that halofuginone inhibits cell proliferation of ULs with low side effects on normal smooth muscle cells, and AKT/mTOR signaling pathway was inactivated meanwhile.

Keywords: AKT; Uterine leiomyomas; apoptosis; cell cycle; halofuginone.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Female
  • Humans
  • Leiomyoma* / drug therapy
  • Leiomyoma* / metabolism
  • Leiomyoma* / pathology
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / pharmacology
  • TOR Serine-Threonine Kinases / therapeutic use
  • Uterine Neoplasms* / drug therapy
  • Uterine Neoplasms* / metabolism
  • Uterine Neoplasms* / pathology

Substances

  • halofuginone
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1