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Osthole inhibited TGF β-induced epithelial-mesenchymal transition (EMT) by suppressing NF-κB mediated Snail activation in lung cancer A549 cells.
Cell Adh Migr. 2017 Sep 03; 11(5-6):464-475.CA

Abstract

Epithelial-mesenchymal transition (EMT), the transdifferentiation of epithelial cells into mesenchymal cells, has been implicated in the metastasis and provides novel strategies for cancer therapy. Osthole (OST), a dominant active constituent of Chinese herb Cnidium monnieri, has been reported to inhibit cancer metastasis while the mechanisms remains unclear. Here, we studied the inhibitory effect and mechanisms of OST on TGF-β1-induced EMT in A549 cells. Cells were treated with TGF-β1 in the absence and presence of OST. The morphological alterations were observed with a microscopy. The protein and mRNA expressions were determined by Western blotting and real-time PCR. The protein localization was detected with immunofluorescence. The adhesion, migration, and invasion were determined by Matrigel, wound-healing, and Transwell assays. TGF-β1 treatment induced spindle-shaped alterations of cells, upregulation of N-cadherin, Vimentin, NF-κB p65, and downregulation of E-cadherin. Dysregulated membrane expression and mRNA expression of E-cadherin and N-cadherin were observed after TGF-β1 treatment. TGF-β1 increased abilities of migration and invasion and triggered the nuclear translocation of NF-κB p65. These alterations were dramatically inhibited by OST. Furthermore, PDTC, a NF-κB inhibitor, showed similar effects. In addition, TGF-β1-induced expression of Snail was significantly inhibited by OST and silenced Snail partially reversed TGF-β1-induced EMT biomarkers without affecting NF-κB p-65. In conclusion, OST inhibited TGF-β1-induced EMT, adhesion, migration, and invasion through inactivation of NF-κB-Snail pathways in A549 cells. This study provides novel molecular mechanisms for the anti-metastatic effect of OST.

Authors+Show Affiliations

a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau , China.a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau , China.a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau , China.b Longhua Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai , China.a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28146373

Citation

Feng, Haitao, et al. "Osthole Inhibited TGF Β-induced Epithelial-mesenchymal Transition (EMT) By Suppressing NF-κB Mediated Snail Activation in Lung Cancer A549 Cells." Cell Adhesion & Migration, vol. 11, no. 5-6, 2017, pp. 464-475.
Feng H, Lu JJ, Wang Y, et al. Osthole inhibited TGF β-induced epithelial-mesenchymal transition (EMT) by suppressing NF-κB mediated Snail activation in lung cancer A549 cells. Cell Adh Migr. 2017;11(5-6):464-475.
Feng, H., Lu, J. J., Wang, Y., Pei, L., & Chen, X. (2017). Osthole inhibited TGF β-induced epithelial-mesenchymal transition (EMT) by suppressing NF-κB mediated Snail activation in lung cancer A549 cells. Cell Adhesion & Migration, 11(5-6), 464-475. https://doi.org/10.1080/19336918.2016.1259058
Feng H, et al. Osthole Inhibited TGF Β-induced Epithelial-mesenchymal Transition (EMT) By Suppressing NF-κB Mediated Snail Activation in Lung Cancer A549 Cells. Cell Adh Migr. 2017 Sep 3;11(5-6):464-475. PubMed PMID: 28146373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osthole inhibited TGF β-induced epithelial-mesenchymal transition (EMT) by suppressing NF-κB mediated Snail activation in lung cancer A549 cells. AU - Feng,Haitao, AU - Lu,Jin-Jian, AU - Wang,Yitao, AU - Pei,Lixia, AU - Chen,Xiuping, Y1 - 2017/02/02/ PY - 2017/2/2/pubmed PY - 2018/8/28/medline PY - 2017/2/2/entrez KW - EMT KW - NF-κB KW - Osthole KW - Snail KW - TGF-β1 SP - 464 EP - 475 JF - Cell adhesion & migration JO - Cell Adh Migr VL - 11 IS - 5-6 N2 - Epithelial-mesenchymal transition (EMT), the transdifferentiation of epithelial cells into mesenchymal cells, has been implicated in the metastasis and provides novel strategies for cancer therapy. Osthole (OST), a dominant active constituent of Chinese herb Cnidium monnieri, has been reported to inhibit cancer metastasis while the mechanisms remains unclear. Here, we studied the inhibitory effect and mechanisms of OST on TGF-β1-induced EMT in A549 cells. Cells were treated with TGF-β1 in the absence and presence of OST. The morphological alterations were observed with a microscopy. The protein and mRNA expressions were determined by Western blotting and real-time PCR. The protein localization was detected with immunofluorescence. The adhesion, migration, and invasion were determined by Matrigel, wound-healing, and Transwell assays. TGF-β1 treatment induced spindle-shaped alterations of cells, upregulation of N-cadherin, Vimentin, NF-κB p65, and downregulation of E-cadherin. Dysregulated membrane expression and mRNA expression of E-cadherin and N-cadherin were observed after TGF-β1 treatment. TGF-β1 increased abilities of migration and invasion and triggered the nuclear translocation of NF-κB p65. These alterations were dramatically inhibited by OST. Furthermore, PDTC, a NF-κB inhibitor, showed similar effects. In addition, TGF-β1-induced expression of Snail was significantly inhibited by OST and silenced Snail partially reversed TGF-β1-induced EMT biomarkers without affecting NF-κB p-65. In conclusion, OST inhibited TGF-β1-induced EMT, adhesion, migration, and invasion through inactivation of NF-κB-Snail pathways in A549 cells. This study provides novel molecular mechanisms for the anti-metastatic effect of OST. SN - 1933-6926 UR - https://www.unboundmedicine.com/medline/citation/28146373/Osthole_inhibited_TGF_β_induced_epithelial_mesenchymal_transition__EMT__by_suppressing_NF_κB_mediated_Snail_activation_in_lung_cancer_A549_cells_ L2 - https://www.tandfonline.com/doi/full/10.1080/19336918.2016.1259058 DB - PRIME DP - Unbound Medicine ER -