TY - JOUR
AR - IJCST-2021-1-103
TI - The Pivotal Role of PAO in CDK Inhibitors (Roscovitine and Purvalanol)- Triggered Apoptosis in PUMA Null HCT116 Colon Cancer Cells
AU - Ajda, Coker-Gurkan
AU - Burcu, Ayhan-Sahin
JO - International Journal of Cancer Science and Therapy
PY - 2021
DA - Wed 04, Aug 2021
SN - 
DO - http://dx.doi.org/10.31487/j.IJCST.2021.01.03
UR - https://www.sciencerepository.org/the-pivotal-role-of-pao-in-cdk-inhibitors_IJCST-2021-1-103 
KW - Puma, colon cancer, CDK inhibitors, polyamine, apoptosis
AB - Background: Cycline-dependent kinase inhibitors (CDKi); roscovitine and purvalanol, are promising anti-cancer drugs due to their strong anti-proliferative effectiveness due to activation of PA catabolism. Besides 
transforming acetylated spermine and spermidine into spermidine and putrescine, respectively, polyamine 
oxidase (PAO) also generates hydrogen peroxide in high concentrations as a by-product. PAO was assumed 
as a pivotal key molecule during drug-induced apoptosis in cancer cells. Our aim is to reveal the role of 
PAO action in CDKi-triggered apoptosis in Puma knock-out HCT116 colon cancer cells. 
Methods: HCT116 wt and HCT116 Puma-/-
cells were treated with Roscovitine and Purvalanol and cell 
viability and apoptosis were determined. Protein was isolated from treated and untreated cells and key 
molecules of cell cycle control and polyamine pathways were investigated at translational level. Polyamine 
content was determined by HPLC for all conditions. MDL-72527 was used as a PAO inhibitor and apoptotic 
cell death was analysed. 
Results: Roscovitine and purvalanol induced apoptosis and increased the cytotoxic responses in HCT116 
wt and HCT116 Puma-/-
colon carcinoma cell lines by modulating CDK1, 4, cyclin-B1, D3. Both, CDKi 
altered intrinsic apoptotic pathways in HCT116 wt. Whereas, drug-induced apoptosis occurred caspase-independent in Puma-/-
colon cancer cells. Roscovitine and purvalanol up-regulated polyamine catabolic 
enzymes, whereas CDK inhibitors decreased the polyamine levels in HCT116 wt and HCT116 Puma-/-
colon 
cancer cells. In addition, PAO inhibitor MDL72527 prevented drug-induced apoptosis. 
Conclusion: PAO expression profile might be a critical target in CDK inhibitors-triggered apoptosis in 
HCT116 colorectal cancer cells. Thus, MAPK signaling pathway relations with cell cycle and polyamine 
catabolic pathway investigations are in progress.