Metformin and asarone inhibit HepG2 cell proliferation in a high glucose environment by regulating AMPK and Akt signaling pathway.

Das, Bhrigu Kumar; Knott, Rachel M.; Gadad, Pramod C.

Abstract

Background: Metabolic dysregulation is one of the hallmarks of tumor cell proliferation. Evidence indicates the potential role of the 5?adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B/Akt signaling pathway in regulating cell proliferation, survival, and apoptosis. The present study explores the effect of metformin HCl and the combination of ?- and ?-asarone on the proliferation of HepG2 cells in the presence of high glucose levels simulating the diabetic-hepatocellular carcinoma (HCC) condition. Results: The metformin and asarone reduced HepG2 cell viability in a dose-dependent manner and induced morphological changes as indicated by methyl thiazolyl tetrazolium (MTT) assay. The metformin and asarone arrested the cells at the G0/G1 phase, upregulated the expression of AMPK, and downregulated Akt expression in high glucose conditions as identified by the flow cytometry technique. Further, the upregulated AMPK led to a decrease in the expression of phosphoenolpyruvate carboxykinase-2 (PCK-2) and sterol regulatory element-binding protein-1 (SREBP-1). Conclusion: The anti-proliferative effect of metformin and asarone in the diabetic-HCC condition is mediated via AMPK and Akt pathway.

Citation

DAS, B.K., KNOTT, R.M. and GADAD, P.C. 2021. Metformin and asarone inhibit HepG2 cell proliferation in a high glucose environment by regulating AMPK and Akt signaling pathway. Future journal of pharmaceutical sciences [online], 7, article 43. Available from: https://doi.org/10.1186/s43094-021-00193-8

• Journal Article Type: Article
• Acceptance Date: Jan 21, 2021
• Online Publication Date: Feb 12, 2021
• Publication Date: Dec 31, 2021
• Deposit Date: Mar 5, 2021
• Publicly Available Date: Mar 5, 2021
• Journal: Future Journal of Pharmaceutical Sciences
• Print ISSN: 2314-7253
• Publisher: SpringerOpen
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Article Number: 43
• DOI: https://doi.org/10.1186/s43094-021-00193-8
• Keywords: Asarone; Metformin HCI; HepG2 cells; High glucose; AMPF; Akt
• Public URL: https://rgu-repository.worktribe.com/output/1240105