Gomisin N exerts anti-liver cancer effects and regulates pi3k-akt and mtor-ulk1 pathways in vitro

Pei Li Zhu, Dick Fai Lam, Jun Kui Li, Xiuqiong FU, Cheng Le Yin, Ji Yao Chou, Ya Ping Wang, Yu Xi Liu, Ying Jie Chen, Jia Ying Wu, Ying Wu, Jing Xuan Bai, Chun Liang, Zhiling YU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.

Original languageEnglish
Pages (from-to)1267-1271
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume43
Issue number8
DOIs
Publication statusPublished - 2020

Scopus Subject Areas

  • Pharmacology
  • Pharmaceutical Science

User-Defined Keywords

  • Apoptosis
  • Autophagy
  • Gomisin N
  • Liver cancer
  • Mammalian target of rapamycin (mTOR)
  • Phosphatidylinositol 3-kinase (PI3K)-Akt

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