Stellettin B Induces G1 Arrest, Apoptosis and Autophagy in Human Non-small Cell Lung Cancer A549 Cells via Blocking PI3K/Akt/mTOR Pathway.
Stellettin B Induces G1 Arrest, Apoptosis and Autophagy in Human Non-small Cell Lung Cancer A549 Cells via Blocking PI3K/Akt/mTOR Pathway.
复制标题
Stellettin B 通过阻断 PI3K/Akt/mTOR 通路诱导人非小细胞肺癌 A549 细胞 G1 期阻滞、凋亡和自噬
DOI：
10.1038/srep27071
复制
发表时间：
2016-05-31
影响因子：
4.6
通讯作者：
Kong D
中科院分区：
文献类型：
--
作者：
Wang R;Zhang Q;Peng X;Zhou C;Zhong Y;Chen X;Qiu Y;Jin M;Gong M;Kong D
迄今为止，尚无针对非小细胞肺癌（NSCLC）疗效显着提高的抗肿瘤药物。海洋生物是具有多种活性的新型化合物的丰富来源。我们从海洋海绵 Jaspis stellifera 中分离出 stellettin B (Stel B)，并证明其在低浓度下可诱导人 NSCLC A549 细胞中的 G1 期阻滞、细胞凋亡和自噬。 Stel B 导致的 G1 期停滞可能归因于细胞周期蛋白 D1 的减少和 p27 表达的增强。细胞凋亡的诱导可能与PARP的裂解和ROS生成的增加有关。此外，我们通过使用单丹磺酰尸胺 (MDC) 染色、透射电子显微镜 (TEM)、串联 mRFP-GFP-LC3 荧光显微镜以及 LC3B、p62 和 Atg5 自噬标记物的蛋白质印迹检测等多种测定法证明 Stel B 诱导 A549 细胞中的自噬。同时，Stel B 抑制 PI3K-p110 的表达，以及 PDK1、Akt、mTOR、p70S6K 以及 GSK-3β 的磷酸化，表明阻断 PI3K/Akt/mTOR 通路与上述抗肿瘤活性相关。总之，我们的研究结果表明 Stel B 通过靶向 PI3K/Akt/mTOR 通路对 NSCLC 具有抗肿瘤潜力。
Until now, there is not yet antitumor drug with dramatically improved efficacy on non-small cell lung cancer (NSCLC). Marine organisms are rich source of novel compounds with various activities. We isolated stellettin B (Stel B) from marine sponge Jaspis stellifera, and demonstrated that it induced G1 arrest, apoptosis and autophagy at low concentrations in human NSCLC A549 cells. G1 arrest by Stel B might be attributed to the reduction of cyclin D1 and enhancement of p27 expression. The apoptosis induction might be related to the cleavage of PARP and increase of ROS generation. Moreover, we demonstrated that Stel B induced autophagy in A549 cells by use of various assays including monodansylcadaverine (MDC) staining, transmission electron microscopy (TEM), tandem mRFP-GFP-LC3 fluorescence microscopy, and western blot detection of the autophagy markers of LC3B, p62 and Atg5. Meanwhile, Stel B inhibited the expression of PI3K-p110, and the phosphorylation of PDK1, Akt, mTOR, p70S6K as well as GSK-3β, suggesting the correlation of blocking PI3K/Akt/mTOR pathway with the above antitumor activities. Together, our findings indicate the antitumor potential of Stel B for NSCLC by targeting PI3K/Akt/mTOR pathway.