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A multi-targets drug, BAI induces apoptosis in various human cancer cells through modulation of Bcl-xL protein

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Author(s)
Shin KimDong Eun KimTaeg Kyu KwonJinho LeeJong-Wook Park
Keimyung Author(s)
Kim, ShinKwon, Taeg KyuPark, Jong Wook
Department
Dept. of Immunology (면역학)
Institute for Medical Science (의과학연구소)
Journal Title
International Journal of Oncology
Issued Date
2016
Volume
49
Issue
6
Keyword
BAIBcl-xLBaxp53PUMAmitochondrial membranepotentialapoptosis
Abstract
Previous studies have demonstrated the anticancer effects of the newly developed cyclin-dependent kinase inhibitor BAI in various cancer cells. However, the molecular mechanisms of the cellular effects induced by BAI have not been fully elucidated. The objective of this study was to investigate the mechanisms underlying the regulation of B cell lymphoma-2 (Bcl-2) family proteins in BAI-induced apoptosis of cancer cells. BAI induced poly(ADP-ribose) polymerase cleavage and DEVDase activation dose- and time-dependently. However, BAI-induced apoptosis was not involved in reactive oxygen species generation or mitogen-activated protein kinases pathways. On the other hand, BAI reduced the mitochondrial membrane potential (∆ψm) dose- and time-dependently, and induced the release of apoptosis-inducing factor (AIF) and cytochrome c from mitochondria in A549 and Caki cells. Furthermore, BAI-induced apoptosis was strongly associated with downregulation of B-cell lymphoma-extra large (Bcl-xL), but not Bcl-2, and BAI modulated the interactions among p53 and Bcl-2 family proteins in human cancer cells. Taken together, these results revealed that the regulations of Bcl-2 family proteins are correlated with BAI-induced apoptosis, suggesting that BAI is a potential multi-target agent of cancer.
Keimyung Author(s)(Kor)
김신
권택규
박종욱
Publisher
School of Medicine (의과대학)
Citation
Shin Kim et al. (2016). A multi-targets drug, BAI induces apoptosis in various human cancer cells through modulation of Bcl-xL protein. International Journal of Oncology, 49(6), 2620–2628. doi: 10.3892/ijo.2016.3758
Type
Article
ISSN
1019-6439
Source
https://www.spandidos-publications.com/10.3892/ijo.2016.3758
DOI
10.3892/ijo.2016.3758
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/41036
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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