Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling.
Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling.
复制标题
DOI：
10.2147/dddt.s91116
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kashfi K
中科院分区：
文献类型：
--
作者：
Kodela R;Nath N;Chattopadhyay M;Nesbitt DE;Velázquez-Martínez CA;Kashfi K
结直肠癌（CRC）是美国男性和女性中第二大癌症死亡原因，也是第三大常见癌症。已知核因子κ B（NF-κB）在CRC中被激活，并且与其发生和进展密切相关。因此，活化的NF-κB构成了这类恶性肿瘤药物开发的真正靶点。许多流行病学和干预性研究已经确定非甾体抗炎药（NSAID）作为一种可行的化学预防策略，对CRC。我们以前的研究表明，几种新型的硫化氢释放NSAID是有前途的抗癌药物，是更安全的NSAID衍生物。在这项研究中，我们研究了一种新的H2S-释放napolipen（HS-NAP），它具有作为一种心血管安全的非甾体抗炎药的剧目，其对细胞增殖，细胞周期相变和细胞凋亡的影响，使用HT-29人结肠癌细胞的生长抑制作用。我们还研究了其作为异种移植小鼠模型中的化学预防剂的效果。HS-NAP通过诱导HT-29细胞G 0/G1期阻滞和凋亡抑制HT-29细胞的生长，下调NF-κB的表达。小鼠中的肿瘤异种移植物的体积显著减小。肿瘤质量的减少与体内细胞增殖减少、凋亡诱导和NF-κB水平降低相关。因此，HS-NAP在CRC中显示出强大的抗癌潜力。
Colorectal cancer (CRC) is the second leading cause of death due to cancer and the third most common cancer in men and women in the USA. Nuclear factor kappa B (NF-κB) is known to be activated in CRC and is strongly implicated in its development and progression. Therefore, activated NF-κB constitutes a bona fide target for drug development in this type of malignancy. Many epidemiological and interventional studies have established nonsteroidal anti-inflammatory drugs (NSAIDs) as a viable chemopreventive strategy against CRC. Our previous studies have shown that several novel hydrogen sulfide-releasing NSAIDs are promising anticancer agents and are safer derivatives of NSAIDs. In this study, we examined the growth inhibitory effect of a novel H2S-releasing naproxen (HS-NAP), which has a repertoire as a cardiovascular-safe NSAID, for its effects on cell proliferation, cell cycle phase transitions, and apoptosis using HT-29 human colon cancer cells. We also investigated its effect as a chemo-preventive agent in a xenograft mouse model. HS-NAP suppressed the growth of HT-29 cells by induction of G0/G1 arrest and apoptosis and downregulated NF-κB. Tumor xenografts in mice were significantly reduced in volume. The decrease in tumor mass was associated with a reduction of cell proliferation, induction of apoptosis, and decreases in NF-κB levels in vivo. Therefore, HS-NAP demonstrates strong anticancer potential in CRC.