English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Chemopreventive agents generate oxidative stress, which culminates in cell death and may be part of a general mechanism of chemoprevention. The redox-responsive cyclooxygenase (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-donating 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 O 2  − ·, had the same effect. Inhibition of caspases and  cox-2  knockdown showed that COX-2 did not participate in reactive oxygen species (ROS) generation or cell death induction in response to NO-ASA. Our results support three potentially useful ideas: (i) the concept that ROS are a critical component of the action of chemopreventive agents; (ii) the notion that COX-2 may not be an ideal target for chemoprevention and (iii) 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.

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