Department of Experimental Medicine and Oncology University of Torino, Cso Raffaello, 30-10125 Torino, Italy.
Anticancer Res. 2010 Jul;30(7):2659-66.
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 beta-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.
先前已经表明，塞来昔布的一种新型亚硝基氧基衍生物在人结肠癌细胞中具有抗增殖和促凋亡作用。本研究的目的是阐明这些生物学特性是否依赖于 COX-2 抑制和/或 NO 释放。因此，将该衍生物分解为母体化合物塞来昔布和 NO 供体苄基硝酸盐，并在 COX-2 阳性（HT-29）和阴性（SW-480）结肠癌细胞中测试每种物质的生物学作用。主要发现是，硝基-氧基衍生物在 HT-29 细胞中的行为与 COX-2 和 ERK/MAPK 抑制以及诱导凋亡方面与塞来昔布相似，而苄基硝酸盐则没有这种作用。有趣的是，β-连环蛋白系统被硝基-氧基衍生物以及单独的苄基硝酸盐激活的强度比母体化合物塞来昔布更强，表明 NO 可能具有调节作用。在 SW480 细胞中，这些活性明显较弱，表明在调节这些参数时存在 COX-2 依赖性机制。
