Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells
Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells
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Elephantopinolide A-P、来自 Elephantopus scaber 的吉马烷型倍半萜内酯诱导肝细胞癌细胞凋亡、自噬和 G2/M 期阻滞
DOI：
10.1016/j.ejmech.2020.112362
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发表时间：
2020-07-15
影响因子：
6.7
通讯作者：
Song, Shao-Jiang
中科院分区：
文献类型：
--
作者：
Bai, Ming;Chen, Jing-Jie;Song, Shao-Jiang
Elephantopus scaber 的色谱纯化产生了 16 种新的香叶兰型倍半萜内酯 (1-16)，命名为elephantopinolide A-P，以及一种已知的类似物 (17)。它们的结构通过综合光谱分析、单晶 X 射线衍射以及实验和计算的 ECD 光谱之间的比较得到证实。采用MTT法筛选其对Hep3B和HepG2细胞的肝细胞抑制活性，并考察其构效关系。结果显示10（IC50值为2.83μM和1.98μM）比索拉非尼更有效。潜在机制研究表明，10 可以显着诱导细胞凋亡，伴随着 ROS 产生增加和线粒体膜电位降低，导致 Hep3B 和 HepG2 细胞自噬和 G2/M 期细胞停滞。此外，包括 MAPK 和 AKT 在内的信号通路可能在 10 诱导的肝细胞癌细胞死亡中发挥重要作用。 (C) 2020 Elsevier Masson SAS。版权所有。
Chromatographic purification of Elephantopus scaber led to 16 new germacrane-type sesquiterpene lactones (1-16), named elephantopinolide A-P, along with a known analogue (17). Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison between the experimental and calculated ECD spectra. Their hepatocellular inhibition activities against Hep3B and HepG2 cells were screened by MTT assay, and the structure-activity relationships were examined. The results revealed that 10 (IC50 value of 2.83 mu M and 1.98 mu M) is more potent than sorafenib. The underlying mechanism study demonstrated that 10 could markedly induce apoptosis accompanied by increased ROS production and decreased mitochondrial membrane potential, resulting in the autophagy and G2/M phase cell arrest in Hep3B and HepG2 cells. Furthermore, signal pathways including MAPKs and AKT may play important roles in 10-induced hepatocellular carcinoma cells death. (C) 2020 Elsevier Masson SAS. All rights reserved.