2. Academic Validation
  3. Gomisin N Exerts Anti-liver Cancer Effects and Regulates PI3K-Akt and mTOR-ULK1 Pathways in Vitro

Gomisin N Exerts Anti-liver Cancer Effects and Regulates PI3K-Akt and mTOR-ULK1 Pathways in Vitro

  • Biol Pharm Bull. 2020;43(8):1267-1271. doi: 10.1248/bpb.b20-00030.
Pei-Li Zhu 1 2 3,  Dick Fai Lam 1,  Jun-Kui Li 1 2 3,  Xiu-Qiong Fu 1 2 3,  Cheng-Le Yin 1 2 3,  Ji-Yao Chou 1 2 3,  Ya-Ping Wang 1 2 3,  Yu-Xi Liu 1 2 3,  Ying-Jie Chen 1 2 3,  Jia-Ying Wu 1 2 3,  Ying Wu 1 2 3,  Jing-Xuan Bai 1 2 3,  Chun Liang 4,  Zhi-Ling Yu 1 2 3
Affiliations

Affiliations

  • 1 Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University.
  • 2 Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University.
  • 3 Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education.
  • 4 Enzynomics Limited.
PMID: 32741948 DOI: 10.1248/bpb.b20-00030
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.

Keywords

apoptosis; autophagy; gomisin N; liver cancer; mammalian target of rapamycin (mTOR); phosphatidylinositol 3-kinase (PI3K)–Akt.

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