Induction of Autophagy and Apoptosis via PI3K/AKT/TOR Pathways by Azadirachtin A in Spodoptera litura Cells

文献类型： 外文期刊

第一作者： Shao, Xuehua

作者： Shao, Xuehua;Lai, Duo;Zhang, Ling;Xu, Hanhong;Lai, Duo;Zhang, Ling

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）

ISSN： 2045-2322

年卷期： 2016 年 6 卷

页码：

收录情况： SCI

摘要： Azadirachtin is one of the most effective botanical insecticides and has been widely used in pest control. Toxicological reports show that azadirachtin can induce apoptosis in various insect cell lines. However, studies of azadirachtin-induced autophagy in cultured insect cells are lacking. This study reports that azadirachtin A significantly inhibits cell proliferation by inducing autophagic and apoptotic cell death in Spodoptera litura cultured cell line ( SL-1 cell). Characteristic autophagolysosome and Atg8-PE ( phosphatidylethanolamine) accumulation were observed by electron microscopy and western blotting, indicating that azadirachtin triggered autophagy in SL-1 cell. Furthermore, azadirachtin inhibited survival signaling by blocking the activation of PI3K, AKT and the down-stream target of rapamycin. Similar to the positive control of starvation, azadirachtin induced the activation of insulin receptor ( InR) via a cellular feedback mechanism. In addition, the autophagy-related 5 ( Atg5), a molecular switch of autophagy and apoptosis, was truncated ( tAtg5) to trigger cytochrome c release into the cytoplasm under azadirachtin stress, which indicated that azadirachtin induced apoptosis through autophagy. Our findings suggest that azadirachtin primarily induced autophagy in SL-1 cell by dysregulating InR-and PI3K/AKT/TOR pathways, then stimulated apoptosis by activating tAtg5.

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