Inhibitory effect of selenomethionine on carcinogenesis in the model of human colorectal cancer in vitro and its link to the Wnt/β-catenin pathway

Selenium compounds have been implicated as anticancer agents; however, the mechanism of their inhibitory action against cancer development has not been extensively investigated. A constitutive activation of the Wnt/beta-catenin pathway is a central event in colorectal carcinogenesis. In this pathway, excessive cell proliferation is initiated by generation of beta-catenin followed by overexpression of proto-oncogenes, such as c-Myc. It is believed that under physiological conditions the level of c-Myc is efficiently controlled by accessibility of the beta-catenin protein through the process of phosphorylation by glycogen synthase kinase 3 beta (GSK-3 beta). Here, we determined whether selenomethionine (SeMet) can inhibit cell growth and affect the Wnt/beta-catenin pathway in the HT-29 human colorectal cancer cells in vitro. The effective cytotoxic doses of SeMet have been selected after 48 h of incubation of this compound with colorectal cancer HT-29 cell line. MTT assay was used to assess cell viability and the protein and mRNA levels of beta-catenin and c-Myc were determined by Western blotting and qPCR, respectively. SeMet potently inhibited growth of HT-29 cells, significantly decreased level of the beta-catenin protein and mRNA concentration, down-regulated the c-Myc gene expression and up-regulated the pro-apoptotic Bax protein level. Moreover, SeMet increased the level of GSK-3 beta phosphorylated at serine 9 (S9) and significantly increased the level of beta-catenin phosphorylated at S33 and S37. We conclude that SeMet suppresses growth of HT-29 colorectal cancer cells by a mechanism linked to the Wnt/beta-catenin pathway, however, degradation of beta-catenin may occur independently of GSK-3 beta catalytic activity and its phosphorylation status.