ReviewTargeting COX-2 expression by natural compounds: A promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy
Graphical abstract
Section snippets
COX-2 inhibitors: limitations and alternative strategies to prevent aberrant COX-2 function
Cyclooxygenase-2 (COX-2) is one of the key enzymes implicated in the modulation of inflammation, and acts by catalyzing the rate-limiting step that leads to the formation of prostaglandins (PGs) from arachidonic acid.
Two other COX isoenzymes, COX-1 and COX-3, are able to catalyze the same kind of reaction. COX-1 is the other significantly important cyclooxygenase family member, which is constitutively expressed in cells and tissues. Exact roles/functions need still to be established for COX-3,
Transcriptional regulation
COX-2 is one of the pro-inflammatory mediators whose expression may be induced at the very early steps of carcinogenesis [30]. This requires its transcriptional activation in pre-neoplastic stages. The prevention of its aberrant expression could, therefore, translate to prevention of the formation of cancer before of its insurgence and may be a potent strategy for cancer prevention. Accordingly, a regular intake of NSAIDs has been the focus of many experimental studies and has been found to
COX-2 transcriptional regulation by natural compounds
The availability of such established cell/tissue models, where COX-2 transcription may be easily triggered, has contributed to the identification of a number of natural occurring compounds acting at this level of COX-2 gene expression (Fig. 1). Those plants extensively used in traditional forms of medicine as well as those used for dietary purposes, whose regular consumption correlated with a lower incidence of cancer, have represented the first natural arsenal from which to extract potentially
Conclusions
Aberrant COX-2 expression is commonly found in different pathologies, where it may play a significant role in disease onset and progression. The fact that COX-2 is expressed at the earliest stages of carcinogenesis makes the targeting of COX-2 a favourable strategy for chemopreventive and chemotherapeutic purposes. Among the pro-inflammatory enzymes COX-2 has the highest number of specific inhibitors available on the market; however, the clinical use of non-selective and selective COX-2
Acknowledgements
C.C. and C.S. are recipients of postdoctoral and doctoral Télévie grants, respectively. Research at the Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC) is financially supported by the Recherche Cancer et Sang foundation, the Recherches Scientifiques Luxembourg association, the Een Haerz fir kriibskrank Kanner association, the Action Lions Vaincre le Cancer association, and by Télévie Luxembourg. Manuscript editing costs were covered by the Fonds National de la Recherche
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