Quercetin Inhibit Human SW480 Colon Cancer Growth in Association with Inhibition of Cyclin D1 and Survivin Expression through Wnt/-Catenin Signaling Pathway

Aim: The Wnt signaling pathway plays a pivotal role in cellular developmental processes and human carcinogenesis. The aim of this study was to investigate the effects of quercetin on the growth of the colon carcinoma cell line and the regulation effect of quercetin on the Wnt/-catenin signaling pathway. Methods: MTT assay was used to determine the reduction of cell viability of quercetin on SW480 cells and clone 26 cells. The apoptotic rate and cell-cycle analysis after treatment with quercetin was determnined by flow cytometry. Effects of quercetin on mRNA expression of cyclin D1 and survivin were detected by semiquantitative RT-PCR. After treatment with quercetin, the protein expression of cyclin D1 and survivin in SW480 cells was analyzed by Western blot analysis. We built a Wnt/-catenin signaling pathway reporter gene model. The regulation effect of quercetin on the Wnt/-catenin signaling transcription was investigated by using this reporter gene model. Results: Quercetin reduced cell viability in a dose- and time-dependent manner in SW480 and clone 26 cells. The percentages of SW480 cells and clone 26 cells at G2/M phase were increased significantly after treatment with 4080 mol/Lquercetin for 48 hours. Quercetin induced the apoptosis of SW480 cells in a dose-dependent manner at the concentration of 20, 40, 60, anf 80 mol/L. However, quercetin only induced the apoptosis of clone 26 cells at the concentration of 80 mol/L. Quercetin downregulated transcriptional activity of -catenin/Tcf in SW480 cells transiently transfected with the TCF-4 reporter gene. Within 24 hours of treatment, a 160-mol/L concentration of quercetin reduced -catenin/Tcf transcriptional activity by about 18-fold. Cyclin D1 and the survivin gene were downregulated markedly by quercetin in a dose-dependent manner at both the transcription and protein expression levels. Conclusion: The results indicate that the molecular mechanism underlying the antitumor effect of quercetin in SW480 colon cancer cells is related to the inhibition of expression of cyclin D1 and survivin as well as the Wnt/-catenin signaling pathway. Therefore, the Wnt/-catenin signaling pathway could be qualified as one of the promising targets for innovative treatment strategies of colorectal cancer.