Eupalinolide J induces apoptosis, cell cycle arrest, mitochondrial membrane potential disruption and DNA damage in human prostate cancer cells

被引:16
|
作者
Wu, Zeqi [1 ]
Xu, Xintong [1 ]
Dai, Lingjie [1 ]
Wang, Yiqi [1 ]
Yang, Bo [1 ]
Zhao, Huajun [1 ]
Lou, Chenghua [1 ]
机构
[1] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China
来源
JOURNAL OF TOXICOLOGICAL SCIENCES | 2020年 / 45卷 / 01期
关键词
Eupalinolide J; Prostate cancer; Apoptosis; Cell cycle; DNA damage response; SESQUITERPENE LACTONES; INHIBITION;
D O I
10.2131/jts.45.15
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:15 / 23
页数:9
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