Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway
文献类型： 外文期刊
作者： Yang, Hairui 1 ; Bai, Xu 1 ; Zhang, Henan 1 ; Zhang, Jingsong 1 ; Wu, Yingying 1 ; Tang, Chuanhong 1 ; Liu, Yanfang 1 ; Y 1 ;
作者机构： 1.Shanghai Acad Agr Sci, Key Lab Appl Mycol Resources & Utilizat, Shanghai Key Lab Agr Genet & Breeding,Minist Agr, Natl Engn Res Ctr Edible Fungi,Inst Edible Fungi, Shanghai 201403, Peoples R China
2.WuXi App Tec Co Ltd, Shanghai 200131, Peoples R China
3.Shihezi Univ, Coll Life Sci, Shihezi 832003, Peoples R China
4.Tibet Agr & Anim Husb Univ, Food Sci Coll, Linzhi 860000, Peoples R China
关键词： antrodin C; apoptosis; autophagy; AKT; mTOR; metabolic stability
期刊名称：MOLECULES （ 影响因子：4.411； 五年影响因子：4.587 ）
ISSN： 1420-3049
年卷期： 2019 年 24 卷 5 期
页码：
收录情况： SCI
摘要： The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and arrested the cell cycle at the G2/M phase via a P53 signaling pathway. Interestingly, phenomena such as autophagosomes accumulation, conversion of the LC3-I to LC3-II, etc., indicated that autophagy could be activated by ADC. The blockage of autophagy-augmented ADC induced inhibition of cell proliferation, while autophagy activation restored cell death, indicating that autophagy had a protective effect against cell death which was induced by ADC treatment. Meanwhile, ADC treatment suppressed both the Akt/mTOR and AMPK signaling pathways. The joint action of both ADC and the autophagy inhibitor significantly increased the death of SPCA-1. An in vitro phase I metabolic stability assay showed that ADC was highly metabolized in SD rat liver microsomes and moderately metabolized in human liver microsomes, which will assist in predicting the outcomes of clinical pharmacokinetics and toxicity studies. These findings imply that blocking the Akt/mTOR signaling pathway, which was independent of AMPK inhibition, could activate ADC-induced protective autophagy in non-small-cell lung cancer cells.
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