N1,N3-bis(3-methoxysalicylidene) diethylenetriamine induces apoptosis in colon cancer HCT-116 cells through inhibiting Wnt1/β-catenin signaling pathway

Objective: The anti-cancer effect and mechanism of N1,N3-bis(3-methoxysalicylidene) diethylenetriamine (Valdien) in HCT-116 cells were assessed in this study. Methods: MTT was used to measure cytotoxicity of the Valdien. The appearance of apoptotic HCT-116 cells was detected by flow cytometry analysis. Apoptosis proteins, caspase family and Bcl-2 family were viewed by Western blotting. The Wnt1/beta-catenin signaling pathway was also examined. HCT-116 cells xenograft serious combined immunodeficiency disease mice were used for the in vivo study. Results: Valdien greatly inhibit HCT-116 cells proliferation in a concentration and time dependent manner and found this effect was associated with apoptosis. Further analysis demonstrated that Valdien induced HCT-116 cells apoptosis by activating the death receptor pathway and regulating cyclin D1 and p21. The expression of anti-apoptotic Bcl-xL, survivin, Bcl-2 was decreased in Valdien treatment groups, whereas the expression of pro-apoptotic Bax protein was increased. Valdien downregulated expression of Wnt1, beta-cateninand, c-myc, while upregulated E-cadherin expression. In addition, HCT-116 cells xenograft mouse model mice were used for the study in vivo. Conclusion: Valdien induced apoptosis in HCT-116 cells in vitro primarily via regulating the Wnt1/beta-catenin signaling pathway and then triggering the activation of the death receptor pathway.