Cyclooxygenase (COX), also known as prostaglandin endoperoxidase or prostaglandin G/H synthase is a rate limiting enzyme involved in the conversion of arachidonic acid to prostaglandins. Two forms of cyclooxygenase ,COX-1 & COX-2 ,have been identified.Cox-1 is constitutively expressed in many tissues , while COX-2 is an inducible enzyme involved in the inhibition of apoptosis , potentiation of cell growth & angiogenesis and as such is a target for drug development. (1) Recently, clinical, cellular and animal experimental studies have indicated it to tumor invasion & metastasis . Ex is a new generation, Cox-2 selective NSAID that stops the production of inflammatory prostaglandins, without stopping the production of prostaglandins that protects the stomach and intestine. The underlying signal transduction pathway is not clarified at the moment but different COX independent mechanisms might contribute to wanted and unwanted effects of this drug. This study examined the proapoptotic effects of Ex in different normal as well as cancerous cell lines. Cell viability was measured by MTT assay and apoptosis was examined by DNA fragmentation & Comet assay. MTT assay on cancerous cell lines especially, Cervical cancer cell line HeLa(COX positive), showed about 50% cell viability at a conc of 200μM. Interestingly, no cytotoxicity was seen with normal cell lines such as NIH3T3,Cos-7 and HEK cells. In conclusion our study shows that in the human cervical cancer cell line HeLa, Ex displays cytostatics, induces apoptosis & cause cell death by DNA damage.The mechanism of action of the drug was seen through Western Blotting with an upregulation of Caspase 3 and inhibition of NF-kB. Similar studies is being carried out on cervical cancer cells,C33A (COX negative) and pancreatic adenocarcinomas,Capan-1 (COX positive ) and MiaPaCa-2 (Cox negative) to determine the effects of Ex on the growth inhibition and induction of apoptosis in these various cell lines.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B107.
Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC