Taxifolin, a natural flavonoid interacts with cell cycle regulators causes cell cycle arrest and causes tumor regression by activating Wnt/ β -catenin signaling pathway

Abstract

Background: New approaches for the prevention of colon cancer perseveres an essential necessity. Though, resistance to existing chemo-preventive drugs is moderately predominant in colon carcinogenesis. Taxifolin (dihydroquercetin) is a flavononol, have shown virile biological activities against few cancers. The current study was designed to investigate and equate antitumor activity of Taxifolin (TAX) in colorectal cancer cell lines and in HCT116 xenograft model in a comprehensive approach. Methods: Two human colorectal cancer cell lines HCT116 and HT29, were used. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MMT) protocol was performed to elucidate the impact of TAX and β- catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis /cell cycle assay was performed. Data interpretation was done with a FACScan (Becton Dickinson, NJ). About 1 × 104 cells per sample were harvested. Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo. Results: We found that TAX induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that administration of TAX to human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, variation in molecules controlling cell cycle operative in the G2 phase of the cell cycle and apoptosis in a concentration dependent approach. Further our results concluded that TAX administration decreases expression of β-catenin gene, AKT gene and Survivin gene and protein expression in in vitro and in vivo. Conclusion: Our findings proposed that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.