3′,5′-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation
3′,5′-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation
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DOI：
10.1016/j.bbrc.2005.01.093
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Raufman, JP
中科院分区：
文献类型：
--
作者：
Karaolis, DKR;Cheng, KR;Raufman, JP
新型环状二核苷酸，3',5'-环状二鸟苷酸，cGpGp (c-di-GMP)，是一种天然存在的小分子，可调节原核生物中的重要信号传导机制。最近，我们表明 c-di-GMP 具有“药物样”特性，并且 cdi-GMP 治疗可能是一种有用的抗菌方法，可减轻金黄色葡萄球菌的毒力和发病机制并预防或治疗感染。在本通讯中，我们报告c-di-GMP（小于或等于50 muM）在体外抑制癌细胞增殖方面具有惊人的特性。 c-di-GMP 抑制基础因子和生长因子（乙酰胆碱和表皮生长因子）诱导的人结肠癌 (H508) 细胞增殖。毒性研究表明，正常大鼠肾细胞和人神经母细胞瘤细胞暴露于生物学相关剂量的 c-di-GMP Lit 中，未显示出致命的细胞毒性。环状二核苷酸，例如c-di-GMP，代表了一种有吸引力的新型“药物平台技术”，不仅可用于开发新的抗菌药物，还可用于开发预防或治疗癌症的新型治疗药物。 (C) 2005 Elsevier Inc. 保留所有权利。
The novel cyclic dinucleotide, 3',5'-cyclic diguanylic acid, cGpGp (c-di-GMP), is a naturally occurring small molecule that regulates important signaling mechanisms in prokaryotes. Recently, we showed that c-di-GMP has "drug-like" properties and that cdi-GMP treatment might be a useful antimicrobial approach to attenuate the virulence and pathogenesis of Staphylococcus aureus and prevent or treat infection. In the present communication, we report that c-di-GMP (less than or equal to50 muM) has striking properties regarding inhibition of cancer- cell proliferation in vitro. c-di-GMP inhibits both basal and growth factor (acetylcholine and epidermal growth factor)-induced cell proliferation of human colon cancel- (H508) cells. Toxicity studies revealed that exposure of normal rat kidney cells and human neuroblastoma cells to c-di-GMP Lit biologically relevant doses showed no lethal cytotoxicity. Cyclic dinucleotides, such as c-di-GMP, represent an attractive and novel "drug-platform technology" that can be used not only to develop new antimicrobial agents, but also to develop novel therapeutic agents to prevent or treat cancer. (C) 2005 Elsevier Inc. All rights reserved.