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

• Authors: Edyta Korbut , Agata Ptak-Belowska , Tomasz Brzozowski
• Languages of publication: EN

Abstracts

EN

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/β-catenin pathway is a central event in colorectal carcinogenesis. In this pathway, excessive cell proliferation is initiated by generation of β-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 β-catenin protein through the process of phosphorylation by glycogen synthase kinase 3β (GSK-3β). Here, we determined whether selenomethionine (SeMet) can inhibit cell growth and affect the Wnt/β-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 β-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 β-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-3β phosphorylated at serine 9 (S9) and significantly increased the level of β-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/β-catenin pathway, however, degradation of β-catenin may occur independently of GSK-3β catalytic activity and its phosphorylation status.

Keywords

EN

colorectal cancer; GSK-3β; Wnt/β-catenin pathway; selenium; selenomethionine

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2018
• Volume: 65
• Issue: 3
• Pages: 359-366

Dates

published

2018

received

2018-04-03

revised

2018-06-10

accepted

2018-06-11

(unknown)

2018-07-18

Contributors

author

Edyta Korbut

• Department of Physiology, Jagiellonian University Medical College, Kraków, Poland

author

Agata Ptak-Belowska

• Department of Physiology, Jagiellonian University Medical College, Kraków, Poland

author

Tomasz Brzozowski

• Department of Physiology, Jagiellonian University Medical College, Kraków, Poland

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Identifiers

DOI

10.18388/abp.2018_2628