Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells

PURPOSE: Colorectal cancer is the third–most commonly occurring cancer in developed countries. Hydroxytyrosol is a potent antioxidant that has several activities, such as oxidative-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 antioxidant 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.