Abstract
2687
Celecoxib (Celebrex®, Pfizer) is a COX-2 selective anti-inflammatory agent used to treat arthritis and other inflammatory processes. It has recently been shown that Celecoxib will decrease the numbers of polyps in patients with Familial Adenomatous Polyposis (FAP) for which it now has FDA approval. Evidence is mounting that Celecoxib will decrease the incidence of breast cancer, and may have usefulness in the treatment of several different tumor types as a chemotherapeutic agent. Several studies have been conducted examining activation of caspase 3 in response to Celecoxib, with no clear results. Thus, we undertook the study of Celecoxib and its affects on 4 tumor cell lines in monolayer, as well as in an agarose suspension method we recently developed. We found that Celecoxib inhibits growth of the BT-20 and MCF-7 breast tumor cell lines as well as A375 melanoma and HT-29 colon carcinoma in monolayer. IC50 values of 60, 55, 45 and 50 μM, respectively, were obtained. We examined caspase expression, and found that Caspases 3, 8, and 9 were not activated in response to treatment at any time point. Staining with Hoechst Stain showed nuclear coalescence, but no DNA fragmentation was found to occur. In the agarose culture methods, where cells grow unattached to plastic, we did not observe cell death but did observe inhibition of mitosis as the treated cells did not form colonies when compared to control. Single cells were seen to be viable as indicated by lack of Trypan blue staining. This suggests that cell death caused by Celecoxib in monolayer does not involve the caspase pathways despite apoptotic appearance, but involves a different pathway altogether and may be unique to the monolayer growth.
- American Association for Cancer Research
Volume 65, Issue 9 Supplement
