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G2 arrest and apoptosis by 2-amino-N-quinoline-8-yl-benzenesulfonamide (QBS), a novel cytotoxic compound

Title
G2 arrest and apoptosis by 2-amino-N-quinoline-8-yl-benzenesulfonamide (QBS), a novel cytotoxic compound
Authors
Kim, YHShin, KJLee, TGKim, ELee, MSRyu, SHSuh, PG
POSTECH Authors
Ryu, SH
Date Issued
Jan-2005
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Abstract
We screened a library of 11,000 small molecular weight chemicals, looking for compounds that affect cell viability. We have identified 2-amino-N-quinoline-8-yl-benzenesulfonamide (QBS) as a potent cytotoxic compound that induces cell cycle arrest and apoptosis. Treatment of Jurkat T cells with QBS increased the levels of cyclin B I as well as phosphorylated-cdc2, which was accompanied by reduced activity of cdc2 kinase, suggesting that QBS may induce cell cycle arrest at G2 phase. Structural analogues of QBS also exhibited similar effects on cell cycle progression and cell viability. Long-term treatment with QBS resulted in DNA fragmentation, cytochrome C release, and PARP cleavage, and an increase in the number of subdiploidy cells, indicative of cellular apoptosis. Moreover, QBS-induced apoptosis was blocked by z-VAD-fmk, a pan-caspase inhibitor. These results suggest that QBS is a novel and potent compound that induces G2 arrest and subsequent apoptosis, implicating it as a putative candidate for chemotherapy. (c) 2005 Elsevier Inc. All rights reserved.
Keywords
library screening; quinolinesulfonamide; DNA damage; G2 arrest; apoptosis; CARBONIC-ANHYDRASE INHIBITORS; DNA-DAMAGE; CELL-CYCLE; NUCLEAR-LOCALIZATION; ANTITUMOR AGENTS; ASSAY; SULFONAMIDES; DEATH; P53; B1
URI
http://oasis.postech.ac.kr/handle/2014.oak/24628
DOI
10.1016/J.BCP.2004.1
ISSN
0006-2952
Article Type
Article
Citation
BIOCHEMICAL PHARMACOLOGY, vol. 69, no. 9, page. 1333 - 1341, 2005-01
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 RYU, SUNG HO
Dept of Life Sciences
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