© The Author 2006. Published by Oxford University Press.
REVIEW |
Cyclooxygenase-2 (COX-2)–Independent Anticarcinogenic Effects of Selective COX-2 Inhibitors
Affiliation of authors: Pharmazentrum Frankfurt, ZAFES, Institut für klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe–Universität Frankfurt, Theodor Stern Kai 7, Frankfurt/Main, Germany
Correspondence to: Sabine Grösch, PhD, Pharmazentrum Frankfurt, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany (e-mail: groesch{at}em.uni-frankfurt.de).
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.
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