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

  • Monireh Sadat Seyyedsalehi Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran.
  • Ali Akbar Saboor-Yaraghi Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran. Department of Immunology ,School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  • Fariba Koohdani Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran.
  • Fatemehsadat Amiri Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
  • Marjan Norouzzadeh Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran.
  • Yas Kalikias Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran.
  • Said Talebi Department of medical genetics Tehran University of Medical Sciences, Tehran, Iran.,
  • Parvin Pasalar Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences,Tehran, Iran
  • Azar Berahmeh Department of Immunology ,School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
  • Farnoosh Shemirani Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran.
  • Maryam Mahmoodi Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran 14155-6447, Iran. Tell: 0098 21 88955805 (internal 109), Fax: 0098 21 88984861.
Keywords: β-catenin, Colorectal cancer, CTNNB1, GSK-3β, HCT-116, Resveratrol, Wnt signaling

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);

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Published
2018-04-30
How to Cite
1.
Seyyedsalehi M, Saboor-Yaraghi AA, Koohdani F, Amiri F, Norouzzadeh M, Kalikias Y, Talebi S, Pasalar P, Berahmeh A, Shemirani F, Mahmoodi M. Resveratrol affects β-catenin and GSK-3β gene expression in Wnt-signalingpathway in HCT-116 human colorectal cancer cells. BCCR. 10(1):22-3.
Section
Original Articles