ROS-dependent Atg4 upregulation mediated autophagy plays an important role in Cd-induced proliferation and invasion in A549 cells. (5th January 2018)

• Record Type: Journal Article
• Authors: Lv, Wei; Sui, Linlin; Yan, Xiaona; Xie, Huaying; Jiang, Liping; Geng, Chengyan; Li, Qiujuan; Yao, Xiaofeng; Kong, Ying; Cao, Jun
• Is Part Of: Chemico-biological interactions. Volume 279(2018)
• Page Start: 136
• Page End: 144
• Publication Date: 2018-01-05
• Subjects: Cadmium -- Atg4 -- ROS -- Cell proliferation -- Autophagy -- Invasion; Cd cadmium -- 3-MA 3-methyladenine -- ROS reactive oxygen species -- NAC N-acetyl cysteine -- A549 cells the human lung glandular cancer cells -- siRNA Small interfering RNA -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide -- GFP green fluorescent protein -- AO acridine orange -- AVOs acidic vesicular organelles -- AVs autophagy vesicles -- DCFH-DA 2′, 7′-dichlorofluorescin diacetate; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.11.013
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Cadmium (Cd) is a toxic heavy metal that is widely used in industry and agriculture. In this study the role of autophagy in Cd-induced proliferation, migration and invasion was investigated in A549 cells. Exposure to Cd (2 μM) significantly increased reactive oxygen species (ROS) production, induced autophagy and enhanced cell growth, migration and invasion in A549 cells. Western blot analysis showed that the expression of autophagy-related proteins, LC3-II, Beclin-1 and Atg4 and invasion-related protein MMP-9 were upregulated in Cd-treated cells. N-acetyl cysteine (NAC) markedly prevented Cd-induced proliferation of A549 cells and the increasing protein level of LC3-II and Atg4. Blocking Atg4 expression by siRNA strongly reduced Beclin-1 and LC3-II protein expression and the number of autophagosome positive cells induced by Cd. Furthermore, Atg4 siRNA increased the number of cells at G0/G1 phase, reduced the number of S and G2/M phase cells, and inhibited Cd-induced cell growth significantly compared with that of Cd-treated Control siRNA cells. 3-MA pretreatment increased the percentage of G0/G1 phase cells, decreased S phase and G2/M phase percentage, and inhibited Cd-induced cell growth remarkably compared with that of only Cd-treated cells. Knocking down Atg4 reduced the number of cells that migrated and invaded through the Matrigel matrix significantly and led to a significant decrease of MMP-9 expression. In addition, in lung tissues of Cd-treated BALB/c mice, the increased expression of LC3-II, Beclin-1 and Atg4 were observed. Taken together, our results demonstrated that ROS-dependent Atg4-mediated autophagy plays an important role in Cd-induced cell growth, migration and invasion in A549 cells. Graphical abstract: Highlights: CdCl2 induced autophagy in A549 cells and in lung tissues of Cd-treated BALB/c mice. CdCl2 induced autophagy mediated by ROS-dependent Atg4 upregulation. CdCl2 -induced autophagy plays an important role in Cd-induced cell cycle, cell growth, migration and invasion in A549 cells.