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Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion, migration, and invasion of lung cancer A549 cells.
Chin J Nat Med. 2017 Jun; 15(6):427-435.CJ

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-1) 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.

Authors+Show Affiliations

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address: xpchen@umac.mo.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28629532

Citation

Feng, Hai-Tao, et al. "Hypaconitine Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Suppresses Adhesion, Migration, and Invasion of Lung Cancer A549 Cells." Chinese Journal of Natural Medicines, vol. 15, no. 6, 2017, pp. 427-435.
Feng HT, Zhao WW, Lu JJ, et al. Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion, migration, and invasion of lung cancer A549 cells. Chin J Nat Med. 2017;15(6):427-435.
Feng, H. T., Zhao, W. W., Lu, J. J., Wang, Y. T., & Chen, X. P. (2017). Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion, migration, and invasion of lung cancer A549 cells. Chinese Journal of Natural Medicines, 15(6), 427-435. https://doi.org/10.1016/S1875-5364(17)30064-X
Feng HT, et al. Hypaconitine Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Suppresses Adhesion, Migration, and Invasion of Lung Cancer A549 Cells. Chin J Nat Med. 2017;15(6):427-435. PubMed PMID: 28629532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion, migration, and invasion of lung cancer A549 cells. AU - Feng,Hai-Tao, AU - Zhao,Wen-Wen, AU - Lu,Jin-Jian, AU - Wang,Yi-Tao, AU - Chen,Xiu-Ping, PY - 2016/12/21/received PY - 2017/6/21/entrez PY - 2017/6/21/pubmed PY - 2018/4/27/medline KW - EMT KW - Hypaconitine KW - NF-κB KW - TGF-β1 SP - 427 EP - 435 JF - Chinese journal of natural medicines JO - Chin J Nat Med VL - 15 IS - 6 N2 - 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-1) 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. SN - 1875-5364 UR - https://www.unboundmedicine.com/medline/citation/28629532/Hypaconitine_inhibits_TGF_��1_induced_epithelial_mesenchymal_transition_and_suppresses_adhesion_migration_and_invasion_of_lung_cancer_A549_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1875-5364(17)30064-X DB - PRIME DP - Unbound Medicine ER -