Induction of apoptosis by streptochlorin isolated from Streptomyces sp in human leukemic U937 cells
Induction of apoptosis by streptochlorin isolated from Streptomyces sp in human leukemic U937 cells
复制标题
DOI：
10.1016/j.tiv.2008.06.010
复制
发表时间：
2008-09-01
影响因子：
3.2
通讯作者：
Choi, Yung Hyun
中科院分区：
文献类型：
--
作者：
Park, Cheol;Shin, Hee Jae;Choi, Yung Hyun
链绿素是由海洋链霉菌产生的小分子。已知具有抗血管生成和抗癌特性。然而，链绿素的作用机制尚不清楚。在这项研究中，我们研究了链二氯林对人白血病 U937 细胞的促凋亡作用。链绿素处理通过诱导细胞凋亡导致浓度和时间依赖性的生长抑制。链菌素诱导的细胞凋亡增加与抗凋亡 Bcl-2 表达下调、促凋亡 Bax 和 FasL 上调、线粒体膜电位 (MMP) 降低、半胱天冬酶激活以及聚 (ADP-核糖) 聚合酶和磷脂酶 C-gamma 1 蛋白降解相关。此外，Caspase-3抑制剂z-DEVD-fmk显着抑制了链二氢酶诱导的细胞毒性作用和细胞凋亡特征，这说明了Caspase-3在此过程中发挥的重要作用。此外，Bcl-2 过表达通过抑制 MMP 崩解和半胱天冬酶激活，显着逆转链二氯素诱导的生长抑制作用，并有效减弱对链二氯素的细胞凋亡反应。然而，Bcl-2 过表达并没有降低链二氯素诱导的 FasL 表达水平升高。总而言之，这些发现表明链二氯素的促凋亡作用是通过激活 U937 细胞中的半胱天冬酶和线粒体来介导的。 (C) 2008 Elsevier Ltd. 保留所有权利。
Streptochlorin is a small molecule that produced by marine Streptomyces sp. that is known to have anti-angiogenic and anti-cancer properties. However, the mechanism by which streptochlorin functions is not well understood. In this study, we investigated the pro-apoptotic effect of streptochlorin in human leukemic U937 cells. Streptochlorin treatment resulted in concentration- and time-dependent growth inhibition by inducing apoptosis. The increase in apoptosis that was induced by streptochlorin was correlated with down-regulation of anti-apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Bax and FasL, a decrease in the mitochondrial membrane potential (MMP), activation of caspases and degradation of poly-(ADP-ribose)polymerase and phospholipase C-gamma 1 protein. In addition, the cytotoxic effects and apoptotic characteristics induced by streptochlorin were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 played in the process. Furthermore, Bcl-2 overexpression significantly reversed the streptochlorin-induced growth inhibitory effects via inhibition of the MMP collapse and caspases activation and effectively attenuated the apoptotic response to streptochlorin. However, the elevated levels of FasL expression induced by streptochlorin were not reduced by Bcl-2 overexpression. Taken together, these findings demonstrate that the pro-apoptotic effect of streptochlorin is mediated through activation of caspases and mitochondria in U937 cells. (C) 2008 Elsevier Ltd. All rights reserved.