The discovery and development of cyclooxygenase-2 inhibitors as potential anticancer therapies.
BACKGROUND
In the past, clinical studies had demonstrated that aspirin and NSAIDs reduce the risk of colorectal cancer. After the discovery of selective prostaglandin-endoperoxide synthase 2 (PTGS2) inhibitors, the further beneficial effects of celecoxib and some other related structures (coxibs) have been demonstrated in both in vivo and in vitro studies.


METHODS
The authors illustrate the role of prostaglandins following the overexpression of PTGS2 (COX-2) in signaling pathways. The authors elucidate the role of coxibs in cell proliferation, apoptosis, angiogenesis and multi-drug resistance and discuss the molecular mechanisms involved. The authors also present the strong evidence related to the usefulness of coxibs in several cancer cell lines.


CONCLUSIONS
There have been a number of PTGS2 (COX-2) selective inhibitors suggested as potential anticancer therapies. In recent years, the development of nanotechnology has also had an impact on chemotherapy. Indeed, nanoparticles of cytotoxic drug carriers have demonstrated potential through their accumulation in cancer cells, and targeting these nanoparticles has been under evaluation. This area could be opened up for coxib development as they are potentially important targets in cancer cells. Further research using celecoxib as a co-drug with PTGS2-overexpressed and PTGS2-independent cancer is still needed.
Tehran University of Medical Sciences, Faculty of Pharmacy, Drug Design & Development Research Center, Department of Medicinal Chemistry , Tehran , Iran moamini@tums.ac.ir.
Mohsen
M
Vosooghi
Mohsen
M
Amini
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases