CR389, a Benzoimidazolyl Pyridinone Analog, Induces Cell Cycle Arrest and Apoptosis via p53 Activation in Human Ovarian Cancer PA-1 CellsCR389, a Benzoimidazolyl Pyridinone Analog, Induces Cell Cycle Arrest and Apoptosis via p53 Activation in Human Ovarian Cancer PA-1 Cells
- Other Titles
- CR389, a Benzoimidazolyl Pyridinone Analog, Induces Cell Cycle Arrest and Apoptosis via p53 Activation in Human Ovarian Cancer PA-1 Cells
- Authors
- 서혜원; 최고운; 이철훈
- Issue Date
- Mar-2015
- Publisher
- 한국미생물·생명공학회
- Keywords
- p53; p21CIP1; Bax; apoptotic induction; cytochrome c; PA-1 cells
- Citation
- Journal of Microbiology and Biotechnology, v.25, no.3, pp.418 - 422
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- Journal of Microbiology and Biotechnology
- Volume
- 25
- Number
- 3
- Start Page
- 418
- End Page
- 422
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/20172
- DOI
- 10.4014/jmb.1412.12080
- ISSN
- 1017-7825
- Abstract
- In the course of screening for novel cell cycle inhibitors and apoptotic inducers, CR389, elucidated as 5-(1H-benzoimidazol-2-yl)-1H-pyridin-2-one, was generated as a new hit compound. Flow cytometric analysis and western blots of PA-1 cells treated with 40 μM CR389 revealed an appreciable cell cycle arrest at the G2/M phase through direct inhibition of the CDK1 complex. In addition, activation of p53 via phosphorylation at Ser15 and subsequent up-regulation of p21CIP1 showed that CR389 also induces p53-dependent-p21CIP1-mediated cell cycle arrest. Furthermore, apoptotic induction in 40 μM CR389-treated PA-1 cells is associated with the release of cytochrome c from mitochondria through up-regulation of the proapoptotic Bax protein, which results in the activation of procaspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, CR389 seems to have multiple mechanisms of antiproliferative activity through p53-mediated pathways against human ovarian cancer cells. Therefore, we conclude that CR389 is a candidate therapeutic agent for the treatment of human ovarian cancer via the activation of p53.
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