PT  - JOURNAL ARTICLE
AU  - CLAUDIA BOCCA
AU  - FRANCESCA BOZZO
AU  - ANDREA BASSIGNANA
AU  - ANTONELLA MIGLIETTA
TI  - Antiproliferative Effect of a Novel Nitro-oxy Derivative of Celecoxib in Human Colon Cancer Cells: Role of COX-2 and Nitric Oxide
DP  - 2010 Jul 01
TA  - Anticancer Research
PG  - 2659--2666
VI  - 30
IP  - 7
4099  - http://ar.iiarjournals.org/content/30/7/2659.short
4100  - http://ar.iiarjournals.org/content/30/7/2659.full
SO  - Anticancer Res2010 Jul 01; 30
AB  - It has been shown previously that a novel nitrooxy derivative of celecoxib exerts antiproliferative and pro-apoptotic effects in human colon cancer cells. The aim of this study was to elucidate whether these biological properties depend on COX-2 inhibition and/or NO release. Therefore, the derivative was decomposed into the parent compound celecoxib and the NO donor benzyl nitrate and the biological role of each was tested in COX-2-positive (HT-29) and -negative (SW-480) colon cancer cells. The main findings were that the nitro-oxy derivative behaved like celecoxib in HT-29 cells in terms of COX-2 and ERK/MAPK inhibition, as well as induction of apoptosis, while the benzyl nitrate had no such effects. Interestingly, the β-catenin system was activated by the nitro-oxy derivative as well as by benzyl nitrate alone more potently than by the parent compound celecoxib, suggesting a possible regulatory role for NO. In SW480 cells, these activities were substantially less pronounced, suggesting the presence of COX-2-dependent mechanisms in the modulation of these parameters.