Effects of hydroxytyrosol on expression of apoptotic genes and activity of antioxidant enzymes in ls180 cells

Abstract

Purpose: Colorectal cancer is the third–most commonly occurring cancer in developed countries. Hydroxytyrosol is a potent antioxidant that has several activities, such as oxida-tive stress control, inhibition of cell proliferation, and induction of apoptosis. In this study, the effect of hydroxytyrosol on the expression of genes effective in apoptosis — BAX, BCL2, CASP3, P53, PPARG, and NFE2L2 — and antioxidant-enzyme activity in LS180 cells of human colorectal cancer was investigated. Methods: The human colorectal cancer cell line LS180 was treated with different concentrations of hydroxytyrosol for 24 hours. Expression of BAX, BCL2, CASP3, NFE2L2, PPARG, and P53 was investigated using real-time PCR. The activity of antioxidant and malondialdehyde enzymes was measured by calorimetric methods. Results: Analysis of gene expression showed that hydroxytyrosol significantly increased the expression of CASP3 and the BAX:BCL2 ratio in treatment groups compared to the control (P<0.05). Also, hydroxytyrosol significantly reduced the expression of the NFE2L2 gene (P<0.05). Calorimetric analysis showed that hydroxytyrosol increased activity of the anti-oxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase in treatment groups significantly more than the control group and reduced thiobarbituric acid–reactive substances on an oxidative stress index (P<0.05). Conclusion: Hydroxytyrosol may induce apoptosis in colorectal cancer cells by increasing the expression of CASP3 gene and increasing the BAX:BCL2 ratio. Also, hydroxytyrosol may increase the activity of antioxidant enzymes and reduce the proliferation of LS180 cells by changing the antioxidant-defense system in cancer cells.