iNOS-selective inhibitors for cancer prevention: promise and progress.
iNOS-selective inhibitors for cancer prevention: promise and progress.
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DOI：
10.4155/fmc.12.168
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发表时间：
2012-11
影响因子：
4.2
通讯作者：
Rao CV
中科院分区：
文献类型：
--
作者：
Janakiram NB;Rao CV
一氧化氮（NO）参与多种生理功能，其在肿瘤发生中的作用已被充分研究。绝大多数人类和实验性肿瘤的进展似乎是由于iNOS产生的NO，进一步受到促炎细胞因子的刺激。相反，在某些情况下，NO与诱导细胞凋亡和肿瘤消退相关。NO的这种二分法在很大程度上是由肿瘤细胞中信号通路的复杂性解释的，肿瘤细胞对NO的反应取决于其浓度。此外，NO通过化学修饰改变许多信号传导途径，例如向靶蛋白添加S-亚硝基硫醇和亚硝基酪氨酸，从而改变各种生物学途径。因此，设计并开发了iNOS抑制剂以抑制包括结肠在内的各种器官部位癌症。在这里，我们审查诱导型一氧化氮合酶的表达，产生的NO，参与改变信号通路，和诱导型一氧化氮合酶选择抑制剂及其可能用于预防和治疗各种癌症。
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.
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