Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Anticancer Agents Med Chem. 2010 Jul;10(6):450-61.

Exploiting cyclooxygenase-(in)dependent properties of COX-2 inhibitors for malignant glioma therapy.

Author information

  • Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California 90089-9094, USA. schontha@usc.edu

Abstract

Cyclooxygenase 2 (COX-2) is frequently found up-regulated during pathological conditions and in cancer, where it is thought to support carcinogenesis and tumor angiogenesis. The development of newer-generation non-steroidal anti-inflammatory drugs (NSAIDs) able to more selectively inhibit cyclooxygenase 2 (COX-2) raised expectations that these agents might be beneficial for cancer prevention and therapy. However, while chemopreventive effects of some selective COX-2 inhibitors have been established, it has remained unpersuasive whether these new NSAIDs, such as celecoxib, rofecoxib or etoricoxib, are able to exert cancer therapeutic effects, i.e., whether they would be beneficial for the treatment of advanced cancers that are already grown and established. This issue was further complicated by findings that celecoxib was able to exert pronounced pro-apoptotic effects in vitro and in vivo in the absence of any apparent involvement of COX-2. In fact, newly synthesized close structural analogs of the celecoxib molecule revealed that it was possible to separate COX-2 inhibitory function from the ability to trigger apoptosis; for example, the analog 2,5-dimethyl-celecoxib (DMC) has lost COX-2 inhibitory function, yet exerts increased cytotoxic potency. This review will summarize pertinent results from the exploratory therapeutic use of NSAIDs, in particular celecoxib, in preclinical and clinical studies of malignant glioma. Several COX-2 independent targets will be presented, and it will be discussed how DMC has helped to delineate their relevance for the surmised COX-2 independent tumoricidal effects of celecoxib.

PMID:
20879982
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Bentham Science Publishers Ltd.
    Loading ...
    Write to the Help Desk