Cell-based studies examining phosphorylation of downstream substrates revealed 20-223 inhibits the kinase activity of CDK5 and CDK2 in multiple CRC cell lines.
Knockdown of FSTL1 in CRC cells with a specific antisense oligonucleotide (AS) reduced expression of regulators of the late G1 phase, such as phosphorylated retinoblastoma protein, E2F-1, cyclin E and phospho-cyclin-dependent kinase-2, and promoted accumulation of cells in the G1 phase of the cell cycle thus resulting in diminished cell proliferation.
To the best of our knowledge, the present study was the first to indicate that ADA inhibits CDK2 and is a potential candidate drug for the treatment of human colorectal cancer.
Our study is the first study that investigates the relationship among variants of CDKN2 p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G risk of CRC and the development and progression in the Turkish population.
Herein, we demonstrated that APRIL depletion by using RNA interference in human colorectal cancer (CRC) COLO 205 and SW480 cells resulted in cell proliferation inhibition and evoked cell cycle arrest in G0/G1 phase and apoptosis, coupled with decrease in CDK2, Cyclin D1, Bcl-2 expression and an increase of p21 and Bax expression.
In summary, these novel results support our hypotheses that the del T poly (T) 8 observed in the 3'-UTR of the CDK2-AP1 gene in human MSI CRC is functionally significant and results in decreased CDK2-AP1 expression.
Western blot analysis revealed that colorectal cancer expressed higher levels of cdk2 and cdc2 than did normal mucosa and that the ratio of the hyperphosphorylated form of pRB was higher in colorectal cancer.