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BAI, A Novel Cyclin-Dependent Kinase Inhibitor Induces Apoptosis in A549 Cells Through Activation of Caspases and Inactivation of Akt

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Author(s)
Shin KimJinho LeeByeong-Churl JangTaeg Kyu KwonJong-Wook Park
Keimyung Author(s)
Kim, ShinKwon, Taeg KyuPark, Jong WookJang, Byeong Churl
Department
Dept. of Immunology (면역학)
Dept. of Molecular Medicine (분자의학)
Journal Title
Journal of Cellular Biochemistry
Issued Date
2013
Volume
114
Issue
2
Keyword
BAIAPOPTOSISCASPASEAKT
Abstract
Previously, we have synthesized a novel cyclin-dependent kinase (CDK) inhibitor, 2-[1,10biphenyl]-4-yl-N-[5-(1,1-dioxo-1l6-isothiazolidin-
2-yl)-1H-indazol-3-yl]acetamide (BAI) and reported its anti-cancer activity in head and neck cancer cells. In this study, we further evaluated
the effect of BAI on growth of various human cancer cell lines, including A549 (nonsmall cell lung cancer), HCT116 (colon), and Caki (kidney).
Profoundly, results of XTT and clonogenic assays demonstrated that BAI at nanomolar concentrations (20–60 nM) inhibited growth of A549,
HCT116, and Caki cells, suggesting the anti-cancer potency. We show that BAI induced a dose-dependent apoptotic cell death in these human
cancer cells, as measured by fluorescence-activated cell sorting (FACS). Interestingly, further biochemical analysis showed that treatment
with BAI at 20nM induced apoptosis in A549 cells in association with activation of caspases, cleavage of phospholipase C-g1 (PLC-g1), and
inhibition of Akt in A549 cells. Importantly, pharmacological inhibition study revealed that pretreatment with z-VAD-fmk, a pan caspase
inhibitor strongly blocked the BAI-induced apoptosis in A549 cells. Transfection analysis with Akt cDNA encoding constitutively active Akt
further addressed the significance of Akt inhibition in the BAI-induced apoptosis in A549 cells. Notably, disruption of the PI3K/Akt pathway
by LY294002, a PI3K/Akt inhibitor potentiated apoptosis in A549 cells by BAI at a subcytotoxic concentration. These findings collectively
suggest that BAI potently inhibits growth of A549, HCT116, and Caki cells, and that the BAI-induced apoptosis in A549 cells is associated with
activation of caspases, and inhibition of Akt.
Keimyung Author(s)(Kor)
김신
권택규
박종욱
장병철
Publisher
School of Medicine
Citation
Shin Kim et al. (2013). BAI, A Novel Cyclin-Dependent Kinase Inhibitor Induces Apoptosis in A549 Cells Through Activation of Caspases and Inactivation of Akt. Journal of Cellular Biochemistry, 114(2), 282–293. doi: 10.1002/jcb.24314
Type
Article
ISSN
0730-2312
Source
http://lps3.onlinelibrary.wiley.com.proxy.dsmc.or.kr/doi/abs/10.1002/jcb.24314
DOI
10.1002/jcb.24314
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33752
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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