Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors.
Nonsteroidal antiinflammatory drugs (NSAIDs) appear to reduce the risk of developing cancer. One mechanism through which NSAIDs act to reduce carcinogenesis is to inhibit the activity of cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in various cancer tissues. Overexpression of COX-2 increases cell proliferation and inhibits apoptosis. However, selective COX-2 inhibitors can also act through COX-independent mechanisms. In this review, we describe the COX-2-independent molecular targets of these COX-2 inhibitors and discuss how these targets may be involved in the anticarcinogenic activities of these selective COX-2 inhibitors. We also compare the concentrations of these inhibitors used in in vitro and in vivo experiments and discuss the implications of the in vitro studies for clinical management of cancer with these drugs.
Grösch
Sabine
S
Pharmazentrum Frankfurt, ZAFES, Institut für klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe, Universität Frankfurt, Theodor Stern Kai 7, Frankfurt/Main, Germany. groesch@em.uni-frankfurt.de
Maier
Thorsten Jürgen
TJ
Schiffmann
Susanne
S
Geisslinger
Gerd
G
D011125:Adenomatous Polyposis Coli / Q000517:prevention & control; D025601:Adenomatous Polyposis Coli Protein / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000201:enzymology* / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011720:Pyrazoles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000187:drug effects
D025601:Adenomatous Polyposis Coli Protein; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; D051176:beta Catenin; C116926:rofecoxib; D051546:Cyclooxygenase 2; D000068579:Celecoxib