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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/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.
cris.lastimport.wos | 2024-04-09T23:30:41Z | |
dc.abstract.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. | pl |
dc.affiliation | Wydział Lekarski : Katedra Fizjologii | pl |
dc.affiliation | Wydział Lekarski : Zakład Fizjologii Doświadczalnej | pl |
dc.cm.date | 2020-12-02 | |
dc.cm.id | 90339 | |
dc.contributor.author | Korbut, Edyta - 115530 | pl |
dc.contributor.author | Ptak-Belowska, Agata - 133237 | pl |
dc.contributor.author | Brzozowski, Tomasz - 128893 | pl |
dc.date.accession | 2020-03-13 | pl |
dc.date.accessioned | 2020-12-02T09:45:04Z | pl |
dc.date.available | 2020-12-02T09:45:04Z | pl |
dc.date.issued | 2018 | pl |
dc.date.openaccess | 0 | |
dc.description.accesstime | w momencie opublikowania | |
dc.description.number | 3 | pl |
dc.description.physical | 359-366 | pl |
dc.description.points | 15 | pl |
dc.description.version | ostateczna wersja wydawcy | |
dc.description.volume | 65 | pl |
dc.identifier.doi | 10.18388/abp.2018_2628 | pl |
dc.identifier.eissn | 1734-154X | pl |
dc.identifier.issn | 0001-527X | pl |
dc.identifier.project | ROD UJ / OP | pl |
dc.identifier.uri | https://ruj.uj.edu.pl/xmlui/handle/item/255819 | |
dc.identifier.weblink | https://ojs.ptbioch.edu.pl/index.php/abp/article/view/2628 | pl |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.rights | Udzielam licencji. Uznanie autorstwa - Na tych samych warunkach 4.0 Międzynarodowa | * |
dc.rights.licence | CC-BY-SA | |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/legalcode.pl | * |
dc.share.type | otwarte czasopismo | |
dc.subtype | Article | pl |
dc.title | Inhibitory effect of selenomethionine on carcinogenesis in the model of human colorectal cancer in vitro and its link to the Wnt/β-catenin pathway | pl |
dc.title.journal | Acta Biochimica Polonica | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |
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