Resveratrol affects β-catenin and GSK-3β gene expression in Wnt-signalingpathway in HCT-116 human colorectal cancer cells

Abstract

Background: 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 in 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.Methods: 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 respectively. Quantitative Real-time PCR examined β-catenin and GSK-3β expression and morphology changes were analyzed.Results: The results showed that, in 25 and 50 μM concentrations, resveratrol reduced β-catenin and GSK-3β expression in 24 h (p-value; 0.001). Gene expressions were found to increase in 48 h and 72 h treatment with resveratrol in the concentrations of 50 and 100 μM respectively (p-value; 0.001).Conclusion: considering our data, it can be concluded that low doses of resveratrol could reduce β-catenin expression, which can affect the Wnt-signaling pathway. 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 while low doses of resveratrol can decrease GSK-3β expression and suppress proliferation.Abbreviations: LEF/TCF, lymphoid enhancing factor/T-cell factor; APC, adenomatous polyposis coli; GSK-3β, glycogen synthase kinase 3B; CK, casein kinase 1; RSV, resveratrol; DMSO, dimethyl sulfoxide; DMEM-F12, Dulbecco's Modified Eagle's Medium F-12; FBS, fetal bovine serum; CIN, chromosomal instability; PI3K, phosphatidylinositol-3-kinase; TGF-β, transforming growth factor-β; GFR, Growth Factor Receptor; KRAS, Kirsten rat sarcoma viral oncogene homolog; PTEN, Phosphatase and tensin homolog; COX, Cytochrome c oxidase; IGF-1R, insulin-like growth factor 1 (IGF-1) receptor; Akt, Protein kinase B (PKB);