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1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one induces cell cycle arrest and apoptosis in HeLa cells by preventing microtubule polymerization

Title
1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one induces cell cycle arrest and apoptosis in HeLa cells by preventing microtubule polymerization
Authors
So Young Kim;Jeong Mi An;Jeong Taeg Seo;Chae Uk Cheong;Sik Kim Du;Han Gil Lee
Issue Date
2011
Journal Title
Biochemical and Biophysicial Research Communications
ISSN
0006-291X
Citation
Biochemical and Biophysicial Research Communications, Vol.408(2) : 287~292, 2011
Abstract
1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) is known as a specific inhibitor of soluble guanylyl cyclase (sGC). Previously, however, ODQ was reported to induce cell death via sGC-dependent and sGC-independent means in a variety of cell types. The aim of this study was to investigate the mechanism by which ODQ induces cell death in HeLa cells. Treatment of HeLa cells with ODQ induced a concentration-dependent decrease in cell viability over the range from 10 to 100 μM. DNA fragmentation and fluorescence-activated cell sorting analysis using annexin V and propidium iodide staining revealed that ODQ triggered apoptosis at concentrations of 50 and 100 μM within 24 to 48 h. The addition of 8-Br-cGMP in the presence of ODQ failed to rescue HeLa cells from death, suggesting that the inhibition of sGC was not responsible for the pro-apoptotic action of ODQ. ODQ arrested the cell cycle at the G2/M phase and caused disassembly of the microtubule network. This process was reversed by dithiothreitol. In addition, ODQ was shown to inhibit the polymerization of purified tubulin, and this was also prevented by dithiothreitol. These results indicate that ODQ inhibits microtubule assembly by direct oxidation of tubulin, induces cell cycle arrest at the G2/M phase, and triggers apoptosis in HeLa cells.
URI
http://www.sciencedirect.com/science/article/pii/S0006291X1100581X

http://ir.ymlib.yonsei.ac.kr/handle/22282913/93036
DOI
10.1016/j.bbrc.2011.04.018
Appears in Collections:
1. 연구논문 > 2. College of Dentistry > Dept. of Oral Biology
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