Antiproliferative Effect of a Novel Nitro-oxy Derivative of Celecoxib in Human Colon Cancer Cells: Role of COX-2 and Nitric Oxide

作者：Bocca Claudia^*; Bozzo Francesca; Bassignana Andrea; Miglietta Antonella

来源：Anticancer Research, 2010, 30(7): 2659-2666.

• Colon cancer
• COX-2
• celecoxib
• nitro-oxy derivative
• beta-catenin
• PI3K/Akt

It has been shown previously that a novel nitrooxy derivative of celecoxib exerts antiproliferative and proapoptotic 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 P-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.

• 出版日期2010-7