α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling
α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling
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α-葎草烯通过抑制 Akt 信号传导抑制肝细胞癌细胞增殖并诱导细胞凋亡
DOI：
10.1016/j.fct.2019.110830
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发表时间：
2019-12-01
影响因子：
4.3
通讯作者：
Yang, Xinzhou
中科院分区：
文献类型：
--
作者：
Chen, Hao;Yuan, Jingquan;Yang, Xinzhou
肝细胞癌（HCC）是一种常见的恶性肿瘤，也是癌症相关死亡的主要原因。α-蛇麻烯（HML）是从飞机草（Eupatorium odoratum L.）我们最近发现HML在体外和体内都具有显著的抗肝癌活性。我们发现HML对肝癌细胞具有细胞毒性，并诱导肝癌细胞线粒体凋亡，促进caspase-3激活和PARP裂解。肝癌细胞显示异常Akt信号以抵抗凋亡。机制上，发现HML抑制Akt活化，随后降低GSK-3和Bad磷酸化，促进凋亡诱导。HML还抑制HCC肿瘤异种移植物中的细胞增殖并增强细胞凋亡，进一步突出了其体内活性。尽管HML对正常肝细胞的细胞毒性极小，但在给予HML的小鼠中观察到体重减轻。总之，这些数据提供了重要的和新的见解HML的抗肝癌效果，通过其抑制Akt的能力，减少肝癌细胞增殖，并增强肝癌细胞凋亡诱导在体外和体内。
Hepatocellular carcinoma (HCC) is a prevalent malignancy and a leading cause of cancer-related mortality. alpha-Humulene (HML) is a natural 11-membered monocyclic terpene with three E-configured double bonds isolated from Eupatorium odoratum L. We recently showed that HML has significant anti-HCC activity in vitro and in vivo. We found that HML was cytotoxic to HCC cells and induced mitochondrial apoptosis of HCC cells, promoting caspase-3 activation and PARP cleavage. HCC cells show abnormal Akt signaling to resist apoptosis. Mechanistically, HML was found to inhibit Akt activation, subsequently decreasing GSK-3 and Bad phosphorylation, promoting apoptotic induction. HML also inhibited cell proliferation and enhanced apoptosis in HCC tumor xenografts further highlighting its activity in vivo. Although HML showed minimal cytotoxicity to normal hepatocytes, weight loss was observed in mice administered HML. Taken together, these data provide important and novel insights into the anti-HCC effects of HML through its ability to inhibit Akt, reduced HCC cell proliferation, and enhanced HCC cell apoptotic induction in vitro and in vivo.