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

Cited by 10 publications

(7 citation statements)

References 59 publications

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“…From the earlier observation linking cell cycle arrest by carotenoids with growth inhibition in cancer cells, 36 we hypothesize that lutein may interrupt cell cycle progression in hyperglycaemic HepG2 cells. In a recent study, antidiabetic drugs such as metformin and arasone exhibited G0/G1 phase arrest with altered expression of allied genetic markers of the cell cycle in hyperglycaemic HCC cells 37 . In our study, we noticed a G2/M phase arrest in lutein‐treated (5 µM) hyperglycaemic HepG2 cells.…”

Section: Discussionsupporting

confidence: 60%

“…In a recent study, antidiabetic drugs such as metformin and arasone exhibited G0/G1 phase arrest with altered expression of allied genetic markers of the cell cycle in hyperglycaemic HCC cells. 37 In our study, we noticed a G2/M phase arrest in lutein-treated (5 µM) hyperglycaemic HepG2 cells. Our consequent studies examining the associated protein expression of the G2/M phase displayed an upregulated expression of pCdk1 and downregulated expression of Cdk2 in lutein-treated cells.…”

Section: Discussionsupporting

confidence: 48%

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Hyperglycaemia‐induced human hepatocellular carcinoma (HepG2) cell proliferation through ROS‐mediated P38 activation is effectively inhibited by a xanthophyll carotenoid, lutein

2021

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Aims: Diabetic population have a twofold to threefold increased risk of developing liver cancer, and hyperglycaemia is a prime causative factor that propends the tumour cells to undergo aggressive metabolic growth. In this study, we aimed to examine the molecular mechanism by which lutein inhibits hyperglycaemiainduced human hepatocarcinoma (HepG2) cell proliferation. Methods:The effect of lutein on high glucose-induced proliferation was measured using the WST-1 reagent. Its effect on intracellular reactive oxygen species (ROS) levels was measured by DCF assay. The effect on the expression of antioxidant enzymes, cell cycle regulatory proteins and intracellular protein kinases was analysed by western blotting. The modulatory effect of lutein on different phases of the cell cycle was analysed by flow cytometry. Results:The data showed that lutein at 5 µM concentration significantly blocked glucose-promoted HepG2 cell proliferation. Suppression of high glucose-induced cell proliferation by lutein was not associated with apoptosis induction, but it was linked with inhibition of hyperglycaemia-mediated elevated ROS and upregulated expression of high glucose-mediated repressed heme oxygenase 1 (HO1). Furthermore, G2/M phase cell cycle arrest and associated phosphorylation of Cdk1 and P53 were found to be linked with suppressed hyperglycaemia-mediated cell proliferation by lutein. In addition, lutein inhibited hyperglycaemia-induced activation of P38 which relates to high glucose-induced ROS-mediated growth suppression and modulated the phosphorylation of Erk, JNK and Akt in hyperglycaemic HepG2 cells. Conclusion:Our findings portray that sufficient intake of lutein may offer a negative impact on diabetes-associated tumour growth.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 48%

Hyperglycaemia‐induced human hepatocellular carcinoma (HepG2) cell proliferation through ROS‐mediated P38 activation is effectively inhibited by a xanthophyll carotenoid, lutein

2021

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“… Schematic representation of the mechanism of potential antidiabetic and cellular antioxidant activities conferred by bioactive compounds such as epicatechin, quercetin, isoliquiritigenin, and formononetin identified by UPLC-MS and HPTLC analysis from a heartwood extract of Pterocarpus marsupium . The identified bioactive compounds relieve oxidative stress and attenuate apoptosis by regulation of ROS in a high glucose, H 2 O 2 -induced environment in HepG2 cells [ 48 , 49 ]. …”

Section: Figurementioning

confidence: 99%

Heartwood Extract of Pterocarpus marsupium Roxb. Offers Defense against Oxyradicals and Improves Glucose Uptake in HepG2 Cells

et al. 2022

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Diabetes mellitus leads to cellular damage and causes apoptosis by oxidative stress. Heartwood extract of Pterocarpus marsupium has been used in Ayurveda to treat various diseases such as leprosy, diabetes, asthma, and bronchitis. In this study, we worked out the mechanism of the antidiabetic potential of methanolic heartwood extract of Pterocarpus marsupium (MPME). First, metabolic profiling of MPME was done using gas chromatography-mass spectrometry (GCMS), ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS), and high-performance thin-layer chromatography (HPTLC) to identify phenols, flavonoids, and terpenoids in MPME. Biological studies were carried out in vitro using the HepG2 cell line. Many antidiabetic compounds were identified including Quercetin. Methanolic extract of MPME (23.43 µg/mL–93.75 µg/mL) was found to be safe and effective in reducing oxyradicals in HepG2 cells. A concentration of 93.75 µg/mL improved glucose uptake efficiently. A significant decrease in oxidative stress, cell damage, and apoptosis was found in MPME-treated HepG2 cells. The study suggests that the heartwood of Pterocarpus marsupium offers good defense in HepG2 cells against oxidative stress and improves glucose uptake. The results show the significant antidiabetic potential of MPME using a HepG2 cell model. The effect seems to occur by reducing oxidative stress and sensitizing the cells towards glucose uptake, hence lowering systemic glucose levels, as well as rescuing ROS generation.

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“…In many studies, a maximum concentration of 20 (3.4 mg mL −1 ) metformin has been used [71][72][73][74][75][76][77][78][79][80] for investigation of cell viability, glucose uptake, and gene expression analysis. We tested a wide range of metformin doses (48.5 µg ml −1 to 100 mg ml −1 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating the effects of Ceylon cinnamon water extract on HepG2 cells for Type 2 diabetes therapy

Azimian

Weerasuriya

Munasinghe

et al. 2023

Cell Biochemistry & Function

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Cinnamon and its extracts have been used as herbal remedies for many ailments, including for reducing insulin resistance and diabetes complications. Type 2 diabetes mellitus (T2DM) is a rapidly growing health concern around the world. Although many drugs are available for T2DM treatment, side effects and costs can be considerable, and there is increasing interest in natural products for managing chronic health conditions. Cinnamon may decrease the expression of genes associated with T2DM risk. The purpose of this study was to evaluate the effects of cinnamon water extract (CWE) compared with metformin on T2DM-related gene expression. HepG2 human hepatoma cells, widely used in drug metabolism and hepatotoxicity studies, were treated with different concentrations of metformin or CWE for 24 or 48 h. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and glucose uptake was compared in untreated and CWE-or metformin-treated cells under highglucose conditions. Finally, total RNA was extracted and analyzed by RNA sequencing (RNA-seq), and bioinformatics analyses were performed to compare the transcriptional effects of CWE and metformin. We found cell viability was better in cells treated with CWE than in metformin-treated cells, demonstrating that CWE was not toxic at tested doses. CWE significantly increased glucose uptake in HepG2 cells, to the same degree as metformin (1.4-fold). RNA-seq data revealed CWE and metformin both induced significantly increased (1.3-to 1.4-fold) glucose uptake gene expression compared with untreated controls. Transcriptional differences between CWE and metformin were not significant. The effects of 0.125 mg mL −1 CWE on gene expression were comparable to 1.5 mg mL −1 (9.5 mM) metformin. In addition, gene expression at 0.125 mg mL −1 CWE was comparable to 1.5 mg mL −1 (9.5 mM) metformin. Our results reveal that CWE's effects on cell viability, glucose uptake, and gene expression in HepG2 cells are comparable to those of metformin, suggesting CWE may be an effective dietary supplement for mitigating T2DMrelated metabolic dysfunction.

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

Cited by 10 publications

References 59 publications

Hyperglycaemia‐induced human hepatocellular carcinoma (HepG2) cell proliferation through ROS‐mediated P38 activation is effectively inhibited by a xanthophyll carotenoid, lutein

Hyperglycaemia‐induced human hepatocellular carcinoma (HepG2) cell proliferation through ROS‐mediated P38 activation is effectively inhibited by a xanthophyll carotenoid, lutein

Heartwood Extract of Pterocarpus marsupium Roxb. Offers Defense against Oxyradicals and Improves Glucose Uptake in HepG2 Cells

Investigating the effects of Ceylon cinnamon water extract on HepG2 cells for Type 2 diabetes therapy

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