Resveratrol inhibits Wnt-signaling by affecting β-catenin and GSK-3β gene expression in HCT-116 human colorectal cancer cells

Colorectal cancer is one of the mostly diagnosed malignancies worldwide. The main risk factors for colorectal cancer include the mutation of tumor suppressor genes or proto-oncogenes and unhealthy lifestyle. Vegetable and fruit consumption with multiple anticancer agents can reduce the risk of colon cancer. Resveratrol, is a natural polyphenolic product that inhibits proliferation and induces apoptosis through several pathways. In this study, the effects of resveratrol on β-catenin (CTNNB1) and GSK-3β expression affecting the Wnt-signaling pathway, were examined and morphology changes were analyzed in colon cancer cells with high levels of β-catenin such as HCT-116.
HCT-116 cells were seeded into 6-well plates and the cells were treated with various concentrations of resveratrol (25, 50 and 100 μM) for 24, 48 and 72 hours. β-catenin and GSK-3β expression were examined by Quantitative Real-time PCR and morphology changes were analyzed.
Our result showed that resveratrol in 25 and 50 μM concentrations of resveratrol reduces β-catenin and GSK-3β expression in 24h (p-value; 0.001). Gene expressions were found to increase in 48h and 72h treatment with resveratrol in the concentration of 50 and 100 μM (p-value; 0.001).
considering our data, we suggest that low doses of resveratrol could reduce β-catenin expression, which can affect the Wnt-signaling pathway. While, high doses can increase the GSK-3β expression, playing a role in the destruction of β-catenin, inhibition of its accumulation in the cytoplasm and nuclear, apoptosis induction and cellular proliferation inhibition. On the other hand, low doses of resveratrol can decrease GSK-3β expression and suppress proliferation.