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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

Authors
 So Young Kim  ;  Jeong Mi An  ;  Han Gil Lee  ;  Sik Kim Du  ;  Chae Uk Cheong  ;  Jeong Taeg Seo 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.408(2) : 287-292, 2011 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2011
MeSH
Apoptosis/drug effects* ; Cell Cycle/drug effects* ; Enzyme Inhibitors/pharmacology* ; Guanylate Cyclase/antagonists & inhibitors* ; HeLa Cells ; Humans ; Microtubules/drug effects* ; Microtubules/metabolism ; Oxadiazoles/pharmacology* ; Oxidation-Reduction/drug effects ; Quinoxalines/pharmacology* ; Tubulin/metabolism
Keywords
ODQ ; Tubulin ; Microtubule ; Cell cycle arrest ; Apoptosis
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X1100581X
DOI
10.1016/j.bbrc.2011.04.018
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Du Sik(김두식)
Kim, So Young(김소영)
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
An, Jeong Mi(안정미)
Lee, Han Gil(이한길)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93036
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