Center for Cancer Prevention & Drug Development, Medical Oncology, Department of Medicine, PCS Oklahoma Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA.
Future Med Chem. 2012 Nov;4(17):2193-204. doi: 10.4155/fmc.12.168.
Nitric oxide (NO) is involved in various physiological functions and its role in tumorigenesis has been well studied. A large majority of human and experimental tumors appear to progress owing to NO resulting from iNOS, further stimulated by proinflammatory cytokines. Conversely, in some cases, NO is associated with induction of apoptosis and tumor regression. This dichotomy of NO is largely explained by the complexity of signaling pathways in tumor cells, which respond to NO very differently depending on its concentration. In addition, NO alters many signaling pathways through chemical modifications, such as the addition of S-nitrosothiols and nitrosotyrosine to target proteins altering various biological pathways. Hence, iNOS inhibitors are designed and developed to inhibit various organ site cancers including the colon. Here, we review iNOS expression, generation of NO, involvement of NO in altering signaling pathways, and iNOS select inhibitors and their possible use for the prevention and treatment of various cancers.
一氧化氮（NO）参与各种生理功能，其在肿瘤发生中的作用已得到充分研究。大多数人类和实验性肿瘤似乎由于 iNOS 产生的 NO 而进展，进一步受到促炎细胞因子的刺激。相反，在某些情况下，NO 与细胞凋亡和肿瘤消退有关。NO 的这种二分法在很大程度上可以通过肿瘤细胞信号通路的复杂性来解释，这些信号通路根据 NO 的浓度而对 NO 的反应非常不同。此外，NO 通过化学修饰改变许多信号通路，例如将 S-亚硝基硫醇和硝基酪氨酸添加到靶蛋白中，从而改变各种生物途径。因此，设计和开发了 iNOS 抑制剂来抑制包括结肠在内的各种器官部位的癌症。在这里，我们回顾了 iNOS 的表达、NO 的产生、NO 在改变信号通路中的作用以及 iNOS 选择性抑制剂及其在预防和治疗各种癌症中的可能用途。
