Involvement of PI3K-AKT-mTOR pathway in protein kinase CKII inhibition-mediated senescence in human colon cancer cells
Language: 
English
Abstract: 

Cellular senescence is a tumor suppression mechanism. We previously reported that CKII downregulation induces senescence in human lung fibroblast IMR-90 and colon cancer HCT116 cells. In this study, potential longevity drugs, including rapamycin, vitamin C, and vitamin E, blocked CKII downregulation-mediated senescence through reduction of reactive oxygen species (ROS) production in HCT116 cells. Since rapamycin is a mammalian target of rapamycin (mTOR) inhibitor, we examined the roles of mTOR and its upstream regulators phosphatidylinositol 3-kinase (PI3K) and AKT in CKII inhibition-mediated senescence. CKII? knock-down or CKII inhibitor treatment strikingly increased phosphorylation of mTOR, p70S6K, an mTOR substrate, and AKT, whereas CKII? overexpression reduced this phosphorylation event. This result indicated that CKII inhibition activated the PI3K-AKT-mTOR pathway. Further, pharmacological inhibition of PI3K and AKT attenuated ROS production and senescence in CKII-downregulated cells. Taken together, these results demonstrate, for the first time, that the PI3K-AKT-mTOR-ROS pathway is necessary for CKII inhibition-mediated cellular senescence.

Author(s): 
Park, Ji Hye
Kim, Jin Joo
Bae, Young-Seuk
Item Type: 
Journal Article
Publication Title: 
Biochemical and Biophysical Research Communications
Journal Abbreviation: 
Biochem. Biophys. Res. Commun.
Publication Date: 
4/19/2013
Publication Year: 
2013
Pages: 
420-425
Volume: 
433
Issue: 
4
ISSN: 
1090-2104
DOI: 
10.1016/j.bbrc.2013.02.108
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23523798

Turabian/Chicago Citation

Ji Hye Park, Jin Joo Kim and Young-Seuk Bae. 4/19/2013. "Involvement of PI3K-AKT-mTOR pathway in protein kinase CKII inhibition-mediated senescence in human colon cancer cells." Biochemical and Biophysical Research Communications 433: 4: 420-425. 10.1016/j.bbrc.2013.02.108.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.bbrc.2013.02.108 | issn = 1090-2104 | volume = 433 | pages = 420-425 | last = Park | first = Ji Hye | coauthors = Kim, Jin Joo, Bae, Young-Seuk | title = Involvement of PI3K-AKT-mTOR pathway in protein kinase CKII inhibition-mediated senescence in human colon cancer cells | journal = Biochemical and Biophysical Research Communications | date = 4/19/2013 | pmid = | pmc = }} </ref>