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

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.

• Authors: Jing Lin, Xiaochun Wu
• Journal: Growth factors (Chur, Switzerland) (Growth Factors) Vol. 40 Issue 5-6 Pg. 212-220 (11 2022) ISSN: 1029-2292 [Electronic] England
• PMID: 36001478 (Publication Type: Journal Article)

Chemical References

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

Topics

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