Skip Navigation



Carcinogenesis Advance Access published online on October 24, 2008
Carcinogenesis, doi:10.1093/carcin/bgn242
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
30/1/93    most recent
bgn242v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Sun, Y.
Right arrow Articles by Rigas, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, Y.
Right arrow Articles by Rigas, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Chemopreventive agents induce oxidative stress in cancer cells leading to COX-2 overexpression and COX-2-independent cell death

Yu Sun*, Jie Chen* and Basil Rigas

Division of Cancer Prevention, Stony Brook University, Stony Brook, NY 11794-5200, USA

Corresponding author: Basil Rigas, Division of Cancer Prevention, Stony Brook University, Life Sciences Building, Room 006, Stony Brook, NY 11794-5200, Tel: 631-632-9035; Fax: 631-632-1992; e-mail: basil.rigas{at}stonybrook.edu

Chemopreventive agents generate oxidative stress, which culminates in cell death and may be part of a general mechanism of chemoprevention. The redox-responsive COX-2, overexpressed during carcinogenesis, has been a target for cancer prevention. To assess the potential link between chemopreventive agents, oxidative stress and COX-2, we studied the chemopreventive sulindac and nitric oxide-releasing aspirin (NO-ASA). Both generated oxidative stress and induced COX-2 in various cell lines, more prominently in dying cells. Two antioxidants and an inhibitor of NADPH oxidase abrogated the induction of COX-2 and cell death. Exogenous xanthine/xanthine oxidase, which produce O2.-, had the same effect. Inhibition of caspases and cox-2 knock-down showed that COX-2 did not participate in ROS generation or cell death induction in response to NO-ASA. Our results support three potentially useful ideas: a) the concept that ROS are a critical component of the action of chemopreventive agents; b) the notion that COX-2 may not be an ideal target for chemoprevention; and c) the possibility that COX-2 may be overexpressed in cancer cells due to their state of oxidative stress. It is conceivable that, if further substantiated, these findings may inform the rational design of chemotherapeutic strategies, in particular the choice of agents in combination approaches.

Key Words: cell death • oxidative stress • cyclooxygenase • NO-aspirin • sulindac • chemoprevention

* These authors contributed equally to the work

Received August 5, 2008; revised October 17, 2008; accepted October 17, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
O. Itano, K. Yang, K. Fan, N. Kurihara, H. Shinozaki, S. Abe, B. Jin, C. Gravaghi, W. Edelmann, L. Augenlicht, et al.
Sulindac effects on inflammation and tumorigenesis in the intestine of mice with Apc and Mlh1 mutations
Carcinogenesis, November 1, 2009; 30(11): 1923 - 1926.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
W. Zou, K. M. Beggs, E. M. Sparkenbaugh, A. D. Jones, H. S. Younis, R. A. Roth, and P. E. Ganey
Sulindac Metabolism and Synergy with Tumor Necrosis Factor-{alpha} in a Drug-Inflammation Interaction Model of Idiosyncratic Liver Injury
J. Pharmacol. Exp. Ther., October 1, 2009; 331(1): 114 - 121.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.