Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion, migration, and invasion of lung cancer A549 cells.
10.1016/S1875-5364(17)30064-X
- Author:
Hai-Tao FENG
1
;
Wen-Wen ZHAO
1
;
Jin-Jian LU
1
;
Yi-Tao WANG
1
;
Xiu-Ping CHEN
2
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address: xpchen@umac.mo.
- Publication Type:Journal Article
- Keywords:
EMT;
Hypaconitine;
NF-κB;
TGF-β1
- MeSH:
A549 Cells;
Aconitine;
analogs & derivatives;
pharmacology;
Active Transport, Cell Nucleus;
drug effects;
Antineoplastic Agents, Phytogenic;
pharmacology;
Cadherins;
analysis;
Cell Adhesion;
drug effects;
Cell Movement;
drug effects;
Dose-Response Relationship, Drug;
Epithelial-Mesenchymal Transition;
drug effects;
Humans;
NF-kappa B;
antagonists & inhibitors;
metabolism;
Neoplasm Invasiveness;
Transforming Growth Factor beta1;
antagonists & inhibitors;
physiology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(6):427-435
- CountryChina
- Language:English
-
Abstract:
Epithelial-mesenchymal transition (EMT) has been implicated in tumor invasion and metastasis and provides novel strategies for cancer therapy. Hypaconitine (HpA), a diester-diterpenoid alkaloid isolated from the root of the Aconitum species, exhibits anti-inflammatory, analgesic, and especially, cardiotoxic activities. Here, we reported the anti-metastatic potentials of HpA in transforming growth factor-β1 (TGF-β1)-induced EMT in lung cancer A549 cells. The cytotoxic effect of HpA was determined by MTT assay. A549 cells were treated with TGF-β1 with or without HpA co-treatment, and the morphological alterations were observed with a microscopy. The expression of E-cadherin, N-cadherin, and NF-κB was determined by both Western blotting and immunofluorescence analyses. The adhesion, migration, and invasion were detected with Matrigel, wound-healing, and transwell assays, respectively. The expression of Snail was determined by Western blotting. The expression of NF-κB p65, IκBα, and p-IκBα in nuclear and cytosolic extracts was assessed by Western blotting. The results showed that low concentration of HpA (<16 μmol·L) had no obvious cytotoxicity to A549 cells. Morphologically, TGF-β1 treatment induced spindle-shaped alteration in the cells. The upregulation of N-cadherin, NF-κB, and Snail and the downregulation of E-cadherin were detected after TGF-β1 treatment. The adhesion, migration and invasion abilities were also increased by TGF-β1. Besides, TGF-β1 induced expression of Snail in a time-dependent manner. Furthermore, TGF-β1 induced nuclear translocation of NF-κB p65. All these alterations were dramatically inhibited by HpA co-treatment. In addition, the NF-κB inhibitor PDTC showed similar inhibitory effect. In conclusion, these results showed that HpA inhibited TGF-β1-induced EMT in A549 cells, which was possibly mediated by the inactivation of the NF-κB signaling pathway, providing an evidence for anti-cancer effect of HpA.
