Document Detail


Role of leukotriene B4 in celecoxib-mediated anticancer effect.
MedLine Citation:
PMID:  20937254     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has anticancer effect on many cancers associated with chronic inflammation by both COX-2-dependent and COX-2-independent mechanisms. The non-COX-2 targets of celecoxib, however, are still a matter of research. Leukotriene B4 (LTB4) has been implicated in prostate and colon carcinogenesis, but little is known about the potential role of LTB4 in celecoxib-mediated anticancer effect. In this study, we evaluated whether LTB4 was involved in celecoxib-mediated inhibitory effect on human colon cancer HT-29 cells and human prostate cancer PC-3 cells. Our data showed that survival of both cell lines was obviously suppressed after celecoxib treatment for 72 h in a concentration-dependent manner. However, only in HT-29 cells, this inhibitory effect could be reversed by LTB4, which promoted survival of HT-29 cells rather than PC-3 cells. Consistent with these results, lioxygenase (LOX) potent inhibitor nordihydroguaiaretic acid (NDGA) had a higher inhibitory effect on HT-29 cells than PC-3 cells. Additionally, ELISA results showed that celecoxib could suppress expression of LTB4 in both cell lines, whereas, inhibition of PGE2 was only detected in HT-29 cells. These results indicate that the anticancer effect of celecoxib is COX-2-independent in HT-29 and PC-3 cells and in HT-29 cells primarily via down-regulating LTB4 production.
Authors:
Peng Gao; Lei Guan; Jie Zheng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-19
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  402     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2010-12-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  308-11     Citation Subset:  IM    
Copyright Information:
Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Pathology and Pathophysiology, School of Medical Science, Southeast University, Nanjing 210009, Jiangsu, People's Republic of China. gp_yaya@163.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects*
Cell Survival / drug effects
Colonic Neoplasms / metabolism
Cyclooxygenase 2 Inhibitors / pharmacology*
Humans
Leukotriene B4 / antagonists & inhibitors,  metabolism*
Lipoxygenase Inhibitors / pharmacology
Male
Nordihydroguaiaretic Acid / pharmacology
Prostatic Neoplasms / metabolism
Pyrazoles / pharmacology*
Sulfonamides / pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cyclooxygenase 2 Inhibitors; 0/Lipoxygenase Inhibitors; 0/Pyrazoles; 0/Sulfonamides; 169590-42-5/celecoxib; 500-38-9/Nordihydroguaiaretic Acid; 71160-24-2/Leukotriene B4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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