Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting ß-Catenin Degradation.
J Microbiol Biotechnol
; 33(9): 1206-1212, 2023 Sep 28.
Article
in En
| MEDLINE
| ID: mdl-37463866
ABSTRACT
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/ß-catenin pathway, which is aberrantly upregulated in colorectal cancer. Kinetin riboside suppressed ß-catenin response transcription (CRT) by accelerating the degradation of intracellular ß-catenin via a proteasomal degradation pathway. Pharmacological inhibition of glycogen synthase kinase-3ß did not affect CRT downregulation. Kinetin riboside decreased the intracellular ß-catenin levels in colorectal cancer cells with mutations in adenomatous polyposis coli (APC) and ß-catenin. Consistently, kinetin riboside repressed expression of c-Myc and cyclin D1, ß-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 ß-catenin degradation and has significant potential as a chemopreventive agent for colorectal cancer cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Beta Catenin
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Microbiol Biotechnol
Year:
2023
Document type:
Article