Abstract
Aims:
Diabetic populations have a two to three-fold increased risk of developing liver cancer, and hyperglycemia is a prime causative factor that propends the tumor cells to undergo aggressive metabolic growth. In this study, we aimed to examine the molecular mechanism by which lutein inhibits hyperglycemia-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 analyzed by western blotting. The modulatory effect of lutein on different phases of the cell cycle was analyzed 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 hyperglycemia-mediated elevated ROS and upregulated expression of high glucose-mediated repressed heme oxygenase 1 (HO1). Further, G2/M phase cell cycle arrest and associated phosphorylation of Cdk1 and P53 were found to be linked with suppressed hyperglycemia-mediated cell proliferation by lutein. In addition, lutein inhibited hyperglycemia-induced activation of P38 which relates to high glucose-induced ROS-mediated growth suppression and modulated the phosphorylation of Erk, JNK, and Akt in hyperglycemic HepG2 cells.
Conclusion:
Our findings portray that sufficient intake of lutein may offer a negative impact on diabetes-associated tumor growth.
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