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

Tehreem, Maradagi and Ravi, Kumar and Ganesan, P. (2022) Hyperglycaemia-induced human hepatocellular carcinoma (HepG2) cell proliferation through ROS-mediated P38 activation is effectively inhibited by a xanthophyll carotenoid, lutein. Diabetic Medicine, 39. e14713.

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Abstract

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 hyperglycaemia-induced 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.

Item Type:	Article
Uncontrolled Keywords:	cell cycle arrest, hepatocarcinoma, hyperglycaemia, lutein, P38
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 14 Carotenoid Chemistry
Divisions:	Molecular Nutrition
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	09 May 2022 09:38
Last Modified:	09 May 2022 09:54
URI:	http://ir.cftri.res.in/id/eprint/15241

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