Essential Oil Derived From Eupatorium adenophorum Spreng. Mediates Anticancer Effect by Inhibiting STAT3 and AKT Activation to Induce Apoptosis in Hepatocellular Carcinoma.

Essential Oil Derived From Eupatorium adenophorum Spreng. Mediates Anticancer Effect by Inhibiting STAT3 and AKT Activation to Induce Apoptosis in Hepatocellular Carcinoma.
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精油源自紫茎泽兰。

DOI:
10.3389/fphar.2018.00483
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发表时间:
2018
影响因子:
5.6
通讯作者:
Yang X
Yang X
中科院分区:
医学2区
文献类型:
--
作者:
Chen H;Zhou B;Yang J;Ma X;Deng S;Huang Y;Wen Y;Yuan J;Yang X

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紫茎泽兰。 (EA)是众所周知的有毒入侵物种。气相色谱-质谱(GC-MS)分析表明,EA精油(EAEO)主要由倍半萜烯组成。然而,EAEO 在肝细胞癌 (HCC) 中的药理学价值仍未得到充分探索。在此,我们研究了 EAEO 的抗 HCC 活性,并探讨了 EAEO 诱导细胞凋亡的潜在机制。 MTT法显示EAEO抑制HCC细胞增殖,对正常肝细胞毒性很小。伤口愈合和 FACS 检测显示 EAEO 分别抑制 HCC 细胞迁移并抑制细胞周期。此外,EAEO促进体外HCC细胞凋亡,并且EAEO处理抑制HepG2异种移植物的生长并增强HepG2荷瘤裸鼠中异种移植物的凋亡核。从机制上讲,EAEO 显着降低 Bcl-2/Bax 的比率,并导致 caspase-9 和 -3 的激活。 EAEO还降低了Grp78的表达,从而缓解了caspase-12和-7的抑制。同时,EAEO 抑制 STAT3 和 AKT 的磷酸化,表明其具有抗 HCC 潜力。总之,我们确定 EAEO 治疗通过激活线粒体和内质网中的凋亡信号通路促进 HCC 凋亡,并抑制 HCC 细胞中 STAT3 和 AKT 的活性。
Eupatorium adenophorum Spreng. (EA) is a well-known noxious invasive species. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the essential oil derived from EA (EAEO) is mainly composed of sesquiterpenes. However, the pharmacological value of EAEO in hepatocellular carcinoma (HCC) remains largely unexplored. Herein, we investigated the anti-HCC activities of EAEO, and explored the potential mechanisms of EAEO-induced apoptosis. An MTT assay showed that EAEO inhibited HCC cell proliferation with little toxicity on normal liver cells. Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle, respectively. Moreover, EAEO promoted in vitro HCC cell apoptosis, and EAEO treatment inhibited HepG2 xenografts growth and enhanced apoptotic nucleus of xenografts in HepG2-bearing nude mice. Mechanistically, EAEO significantly decreased the ratio of Bcl-2/Bax and resulted in the activation of caspase-9 and -3. EAEO also reduced the expression of Grp78, which in turn relieved the inhibition of caspase-12 and -7. Meanwhile, EAEO suppressed the phosphorylation of STAT3 and AKT, indicative of its anti-HCC potential. In summary, we determined that EAEO treatment promoted HCC apoptosis via activation of the apoptotic signaling pathway in mitochondria and endoplasmic reticulum, as well as repressed the activity of STAT3 and AKT in HCC cells.
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