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.

doi:10.1186/s43094-021-00193-8

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.

Authors

Bhrigu Kumar Das

Rachel M. Knott

Pramod C. Gadad

Abstract

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 α- and β-asarone on the proliferation of HepG2 cells in the presence of high glucose levels simulating the diabetic-hepatocellular carcinoma (HCC) condition. 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). 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
Electronic ISSN	2314-7253
Publisher	Springer
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