Deoxyelephantopin, a germacrane-type sesquiterpene lactone from Elephantopus scaber, induces mitochondrial apoptosis of hepatocarcinoma cells by targeting Hsp90a in vitro and in vivo
Deoxyelephantopin, a germacrane-type sesquiterpene lactone from Elephantopus scaber, induces mitochondrial apoptosis of hepatocarcinoma cells by targeting Hsp90a in vitro and in vivo
复制标题
Deoxyelephantopin 是一种来自 Elephantopus scaber 的germacrane型倍半萜内酯，在体外和体内通过靶向 Hsp90α 诱导肝癌细胞线粒体凋亡
DOI：
10.1002/ptr.7654
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发表时间：
2022-11-24
影响因子：
7.2
通讯作者：
Yao, Guo-Dong
中科院分区：
文献类型：
--
作者：
Chen, Jing-Jie;Yan, Qiu-Lin;Yao, Guo-Dong
Hepatocellular carcinoma has been known as the most frequent subtype of liver cancer with a high rate of spread, metastases, and recurrence, also dismal treatment effects. However, effective therapies for HCC are still required. Nowadays, natural products have been known as a valuable source for drug discovery. In this research, 44 sesquiterpene lactones isolated from the Elephantopus scaber Linn. (Asteraceae) were tested by MTT assay for the antitumor activities. Deoxyelephantopin (DET) was found to exert significant cytotoxicity on HepG2 and Hep3B cells. Moreover, we found that DET treatment markedly reduced the growth of HCC cells in a concentration-dependent manner, which was better than sorafenib. Furthermore, DET induced mitochondrial dysfunction, oxidative stress, and cellular apoptosis. Additionally, we found that DET and sorafenib synergistically induced apoptosis and mitochondrial dysfunction in HCC cells. DET combined with sorafenib was also efficacious in tumor xenograft model. Molecular docking experiments revealed that DET had a potentially high binding affinity with Hsp90 alpha. Moreover, Drug Affinity Responsive Target Stability assay suggested that DET could directly target Hsp90 alpha. Additionally, the expression of Hsp90 alpha was both decreased in vitro and in vivo. Altogether, this study revealed that DET might be a promising agent for HCC therapy by targeting Hsp90 alpha.
