CR389, a Benzoimidazolyl Pyridinone Analog, Induces Cell Cycle Arrest and Apoptosis via p53 Activation in Human Ovarian Cancer PA-1 Cells
- Title
- CR389, a Benzoimidazolyl Pyridinone Analog, Induces Cell Cycle Arrest and Apoptosis via p53 Activation in Human Ovarian Cancer PA-1 Cells
- Author
- 서혜원
- Keywords
- p53; p21CIP1; Bax; apoptotic induction; cytochrome c; PA-1 cells
- Issue Date
- 2015-03
- Publisher
- 한국미생물생명공학회
- Citation
- JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, v. 25, No. 3, Page. 418-422
- 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.
- URI
- http://kiss.kstudy.com/thesis/thesis-view.asp?key=3311292https://repository.hanyang.ac.kr/handle/20.500.11754/106000
- ISSN
- 1017-7825; 1738-8872
- Appears in Collections:
- RESEARCH INSTITUTE[E](부설연구소) > INSTITUTE OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY(약학기술연구소) > Articles
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