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首页> 外文期刊>Free Radical Biology and Medicine: The Official Journal of the Oxygen Society >Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma.
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Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma.

机译:紫草素是一种来自中国植物的萘醌,它通过活性氧诱导肝癌细胞的凋亡:一种潜在的治疗肝癌的新方法。

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摘要

Although shikonin, a naphthoquinone derivative, has showed anti-cancer activity, its precise molecular anti-tumor mechanism remains to be elucidated. In this study, we investigated the effects of shikonin on human hepatocellular carcinoma (HCC) in vitro and in vivo. Our results showed that shikonin induced apoptosis of Huh7 and BEL7402 but not nontumorigenic cells. ROS generation was detected, and ROS scavengers completely inhibited shikonin-induced apoptosis, indicating that ROS play an essential role. Although the JNK activity was significantly elevated after shikonin treatment, JNK was not linked to apoptosis. However, downregulation of Akt and RIP1/NF-kappaB activity was found to be involved in shikonin-induced apoptosis. Ectopic expression of Akt or RIP1 partly abrogated the effects of shikonin, and Akt inhibitor and RIP1 inhibitor synergistically induced apoptosis in conjunction with shikonin treatment. ROS scavengers blocked shikonin-induced inactivation of Akt and RIP1/NF-kappaB, but Akt or RIP1/NF-kappaB did not regulate ROS generation, suggesting that Akt and RIP1/NF-kappaB signals are downstream of ROS generation. In addition, the results of xenograft experiments in mice were consistent with in vitro studies. Taken together, our data show that shikonin, which may be a promising agent in the treatment of liver cancer, induced apoptosis in HCC cells through the ROS/Akt and RIP1/NF-kappaB pathways.
机译:尽管紫草素是一种萘醌衍生物,已显示出抗癌活性,但其确切的分子抗肿瘤机制仍有待阐明。在这项研究中,我们调查了紫草素在体外和体内对人肝细胞癌(HCC)的影响。我们的结果表明,紫草素可诱导Huh7和BEL7402凋亡,但不能诱导非致瘤细胞。检测到ROS的产生,并且ROS清除剂完全抑制了紫草素诱导的细胞凋亡,表明ROS起着重要的作用。尽管紫草素处理后JNK活性显着升高,但JNK与凋亡无关。然而,发现Akt和RIP1 / NF-kappaB活性的下调与紫草素诱导的细胞凋亡有关。 Akt或RIP1的异位表达部分地取消了紫草素的作用,Akt抑制剂和RIP1抑制剂与紫草素治疗协同协同诱导了细胞凋亡。 ROS清除剂阻止了紫草素诱导的Akt和RIP1 / NF-kappaB失活,但Akt或RIP1 / NF-kappaB不能调节ROS的产生,表明Akt和RIP1 / NF-kappaB信号是ROS产生的下游。此外,小鼠异种移植实验的结果与体外研究一致。综上所述,我们的数据表明,紫草素可能是治疗肝癌的一种有前途的药物,它通过ROS / Akt和RIP1 / NF-kappaB途径诱导HCC细胞凋亡。

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