Eupalinolide J induces apoptosis, cell cycle arrest, mitochondrial membrane potential disruption and DNA damage in human prostate cancer cells
Eupalinolide J induces apoptosis, cell cycle arrest, mitochondrial membrane potential disruption and DNA damage in human prostate cancer cells
复制标题
Eupalinolide J 诱导人前列腺癌细胞凋亡、细胞周期停滞、线粒体膜电位破坏和 DNA 损伤
DOI：
10.2131/jts.45.15
复制
发表时间：
2020-01-01
影响因子：
2
通讯作者：
Lou, Chenghua
中科院分区：
文献类型：
--
作者：
Wu, Zeqi;Xu, Xintong;Lou, Chenghua
泽兰素J（Eupalinergic J，EJ）是从野马追（Eupatorium lindleyanum DC）中分离得到的一个新的倍半萜内酯。在本研究中，我们研究了EJ对人前列腺癌细胞增殖的抗癌活性。MTT结果表明，EJ对PC-3和DU-145细胞具有明显的抑制增殖作用，并呈剂量和时间依赖性。DAPI染色分析表明，这种作用是通过诱导细胞凋亡介导的。流式细胞仪分析表明，EJ处理后，凋亡细胞明显增加，细胞周期阻滞在G 0/G1期，线粒体膜电位（MMP）破坏。同时可见caspase-3和caspase-9的活化。此外，我们的结果表明，γ H2 AX，p-Chk 1和p-Chk 2的表达水平显着上调，表明在EJ处理的前列腺癌细胞中诱导DNA损伤反应。以上结果表明，EJ具有较好的体外抗肿瘤活性。它可能是一个有前途的候选药物，用于临床治疗前列腺癌。
Eupalinolide J (EJ) is a new sesquiterpene lactone isolated from Eupatorium lindleyanum DC. In the present study, we investigated the anti-cancer activity of EJ on cell proliferation in human prostate cancer cells. The MTT results indicated that EJ showed marked anti-proliferative activity in PC-3 and DU-145 cells in a dose- and time-dependent manner. DAPI staining analysis demonstrated that this effect was mediated by induction of cell apoptosis. Flow cytometric analysis indicated a significant increase in apoptotic cells, cell cycle arrest at G0/G1 phase and disruption of mitochondrial membrane potential (MMP) after EJ treatment. Meanwhile, the activation of caspase-3 and caspase-9 was visibly observed. Furthermore, our results demonstrated that the expression levels of gamma H2AX, p-Chk1 and p-Chk2 were significantly up-regulated, suggesting the induction of DNA damage responses in EJ-treated prostate cancer cells. The above results indicated that EJ exhibited effective anti-cancer activity in vitro. It could be a promising candidate agent for the clinical treatment of prostate cancer.