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Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation
Kinetin riboside is a naturally produced cytokinin that displays strong antiproliferative activity in various human cancer cells. However, the mechanism of chemoprevention in colorectal cancer cells has not been elucidated. We used a cell-based reporter system to identify kinetin riboside as an anta...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Society for Microbiology and Biotechnology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580898/ https://www.ncbi.nlm.nih.gov/pubmed/37463866 http://dx.doi.org/10.4014/jmb.2301.01035 |
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author | Nam, TaeKyung Kang, Wonku Oh, Sangtaek |
author_facet | Nam, TaeKyung Kang, Wonku Oh, Sangtaek |
author_sort | Nam, TaeKyung |
collection | PubMed |
description | Kinetin riboside is a naturally produced cytokinin that displays strong antiproliferative activity in various human cancer cells. However, the mechanism of chemoprevention in colorectal cancer cells has not been elucidated. We used a cell-based reporter system to identify kinetin riboside as an antagonist of the Wnt/β-catenin pathway, which is aberrantly upregulated in colorectal cancer. Kinetin riboside suppressed β-catenin response transcription (CRT) by accelerating the degradation of intracellular β-catenin via a proteasomal degradation pathway. Pharmacological inhibition of glycogen synthase kinase-3β did not affect CRT downregulation. Kinetin riboside decreased the intracellular β-catenin levels in colorectal cancer cells with mutations in adenomatous polyposis coli (APC) and β-catenin. Consistently, kinetin riboside repressed expression of c-Myc and cyclin D1, β-catenin/T-cell factor (TCF)-dependent genes, and inhibited the proliferation of colorectal cancer cells. In addition, kinetin riboside stimulated apoptosis, as measured by an increase in annexin V-FITC-stained cells. These findings suggest that kinetin riboside exerts its anti-cancer activity by promoting β-catenin degradation and has significant potential as a chemopreventive agent for colorectal cancer cells. |
format | Online Article Text |
id | pubmed-10580898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Korean Society for Microbiology and Biotechnology |
record_format | MEDLINE/PubMed |
spelling | pubmed-105808982023-10-18 Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation Nam, TaeKyung Kang, Wonku Oh, Sangtaek J Microbiol Biotechnol Research article Kinetin riboside is a naturally produced cytokinin that displays strong antiproliferative activity in various human cancer cells. However, the mechanism of chemoprevention in colorectal cancer cells has not been elucidated. We used a cell-based reporter system to identify kinetin riboside as an antagonist of the Wnt/β-catenin pathway, which is aberrantly upregulated in colorectal cancer. Kinetin riboside suppressed β-catenin response transcription (CRT) by accelerating the degradation of intracellular β-catenin via a proteasomal degradation pathway. Pharmacological inhibition of glycogen synthase kinase-3β did not affect CRT downregulation. Kinetin riboside decreased the intracellular β-catenin levels in colorectal cancer cells with mutations in adenomatous polyposis coli (APC) and β-catenin. Consistently, kinetin riboside repressed expression of c-Myc and cyclin D1, β-catenin/T-cell factor (TCF)-dependent genes, and inhibited the proliferation of colorectal cancer cells. In addition, kinetin riboside stimulated apoptosis, as measured by an increase in annexin V-FITC-stained cells. These findings suggest that kinetin riboside exerts its anti-cancer activity by promoting β-catenin degradation and has significant potential as a chemopreventive agent for colorectal cancer cells. The Korean Society for Microbiology and Biotechnology 2023-09-28 2023-06-23 /pmc/articles/PMC10580898/ /pubmed/37463866 http://dx.doi.org/10.4014/jmb.2301.01035 Text en Copyright © 2023 by the authors. Licensee KMB https://creativecommons.org/licenses/by/4.0/This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Research article Nam, TaeKyung Kang, Wonku Oh, Sangtaek Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation |
title | Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation |
title_full | Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation |
title_fullStr | Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation |
title_full_unstemmed | Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation |
title_short | Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation |
title_sort | apoptosis of kinetin riboside in colorectal cancer cells occurs by promoting β-catenin degradation |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580898/ https://www.ncbi.nlm.nih.gov/pubmed/37463866 http://dx.doi.org/10.4014/jmb.2301.01035 |
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