Abstract
BackgroundMetabolic 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.ResultsThe 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).ConclusionThe anti-proliferative effect of metformin and asarone in the diabetic-HCC condition is mediated via AMPK and Akt pathway.
Highlights
Metabolic dysregulation is one of the hallmarks of tumor cell proliferation
The combined effect of α- and β-asarone inhibits the cell proliferation The corresponding methyl thiazolyl tetrazolium (MTT) results showed that the cell proliferation of α- or β-asarone was inhibited compared to the untreated cells (p < 0.01) and that the combined effect of α- and β-asarone (0.61 mM + 0.73 mM) was representative flow cytometry histogram events depicting the expression of phosphoenolpyruvate carboxykinase-2 (PCK-2) in normal glucose (NG; 5.5 mM), high glucose (HG; 25 mM), HG
Values represent mean ± SEM of an experiment done in triplicate; one-way analysis of variance (ANOVA) followed by Bonferroni test, where ***p < 0.001 compared to the normal glucose (NG) group and ###p < 0.001 compared to the high glucose (HG) group better (p < 0.05) than the single effect of α- or β-asarone (0.61 mM or 0.73 mM) (Fig. 2)
Summary
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. There are a growing number of studies that propose the 5′adenosine monophosphate-activated protein kinase (AMPK), a highly conserved heterotrimeric serine/ threonine-protein kinase, is a crucial mediator as an energy sensor in all the eukaryotic cells [6]. It plays a vital role in maintaining cellular energy homeostasis in both diabetes and cancer growth [7, 8]. These effects are reported to be mediated through different mechanisms, including the modulation of cell cycle profile, autophagy, apoptosis, de novo fatty acid synthesis, and inhibition of protein synthesis [12, 13]
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