Pterostilbene exerts antitumor activity via the Notch1 signaling pathway in human lung adenocarcinoma cells.
Pterostilbene exerts antitumor activity via the Notch1 signaling pathway in human lung adenocarcinoma cells.
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紫檀芪通过人肺腺癌细胞中的 Notch1 信号通路发挥抗肿瘤活性
DOI：
10.1371/journal.pone.0062652
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yi D
中科院分区：
文献类型：
--
作者：
Yang Y;Yan X;Duan W;Yan J;Yi W;Liang Z;Wang N;Li Y;Chen W;Yu S;Jin Z;Yi D
尽管紫檀芪 (PTE) 已被证明对各种癌症类型具有有效的抗肿瘤活性，但这些活性的分子机制仍不清楚。在本研究中，我们在体外和体内研究了PTE对人肺腺癌的抗肿瘤活性，并探讨了Notch1信号通路在此过程中的作用。 PTE 治疗导致 A549 细胞活力呈剂量和时间依赖性下降。此外，PTE 表现出强大的抗肿瘤活性，这不仅体现在线粒体膜电位 (MMP) 降低和细胞内谷胱甘肽含量下降，还体现在细胞凋亡指数和活性氧 (ROS) 水平的增加。此外，PTE 治疗诱导 Notch1 胞内结构域 (NICD) 蛋白的激活并激活 Hes1。 DAPT（一种 γ 分泌酶抑制剂）和 Notch1 siRNA 阻止 PTE 处理诱导 NICD 和 Hes1 激活，并使细胞对 PTE 处理敏感。 Notch 信号传导的下调还阻止了 PTE 治疗后促生存途径（最显着的是 PI3K/Akt 途径）的激活。总之，肺腺癌细胞可能增强 Notch1 激活，作为响应 PTE 治疗的保护机制。将γ分泌酶抑制剂与PTE治疗相结合可能代表了一种通过抑制癌细胞的生存途径来治疗肺腺癌的新方法。
Although pterostilbene (PTE) has been shown to have potent antitumor activities against various cancer types, the molecular mechanisms of these activities remain unclear. In this study, we investigated the antitumor activity of PTE against human lung adenocarcinoma in vitro and in vivo and explored the role of the Notch1 signaling pathway in this process. PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by a reduced mitochondrial membrane potential (MMP) and a decreased intracellular glutathione content but also by increases in the apoptotic index and the level of reactive oxygen species (ROS). Furthermore, PTE treatment induced the activation of the Notch1 Intracellular Domain (NICD) protein and activated Hes1. DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment. The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment. In summary, lung adenocarcinoma cells may enhance Notch1 activation as a protective mechanism in response to PTE treatment. Combining a gamma secretase inhibitor with PTE treatment may represent a novel approach for treating lung adenocarcinoma by inhibiting the survival pathways of cancer cells.
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影响因子：
4.8
作者：
Sade, H;Krishna, S;Sarin, A
通讯作者：
Sarin, A
Notch-1信号传导促进人非小细胞肺癌细胞中生存素的表达
影响因子：
3.6
作者：
Chen, Yuqing;Li, Dianming;Wang, Xiaojing
通讯作者：
Wang, Xiaojing
影响因子：
5
作者：
Huang, Po-Hsun;Chen, Jia-Shiong;Chen, Jaw-Wen
通讯作者：
Chen, Jaw-Wen
影响因子：
2.2
作者：
Moon, Dora;McCormack, Denise;McFadden, David
通讯作者：
McFadden, David
影响因子：
9.7
作者：
Ren, Xin-Ling;Xu, Yan-Ming;Yang, An-Gang
通讯作者：
Yang, An-Gang