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Natural alkaloid 8-oxo-epiberberine inhibited TGF-β1-triggred epithelial-mesenchymal transition by interfering Smad3
Liu,Xin1; Zhang,Yiying1; ZHOU,Guang Ju2; Hou,Ying1; Kong,Qi3; Lu,Jin Jian1; Zhang,Qingwen1; Chen,Xiuping1
Source PublicationToxicology and Applied Pharmacology

Epithelial-mesenchymal transition (EMT), the transition of epithelial cells into mesenchymal cells, plays important roles in the metastasis of solid tumors. 8-Oxo-epiberberine (OPB) is a natural alkaloid extracted from the roots of Coptis chinensis Franch. In this study, The effect and the underlying mechanism of OPB on EMT in a TGF-β1-induced model and the inhibitory effect of OPB on lung metastasis were investigated. TGF-β1-stimulated lung cancer cells were co-treated with OPB, the morphological changes were examined. The protein expression of EMT biomarkers E-cadherin and N-cadherin was determined by Western blotting and immunofluorescence. The transcription activity of smad2/3 promoter was analyzed by a luciferase reporter assay. The effect of OPB on cell migration, invasion, and adhesion was detected by wound-healing, adhesion, and transwell assays. The in vivo anti-metastatic effect of OPB was evaluated using a 4 T1 cell xenograft mouse model. Results showed that OPB significantly reversed TGF-β1-triggered morphological changes, expression of EMT biomarkers, and migration, adhesion, and invasion. Furthermore, OPB suppressed TGF-β1-induced Smad2/3 activation, Smad3 phosphorylation and nuclear translocation, and interaction of Smad3 with Smad4. Besides, OPB dramatically decreased the metastatic nodules in the lung without affecting the growth of primary tumors. In conclusion, OPB inhibited TGF-β1-induced EMT possibly by interfering with Smad3. OPB might have therapeutic potentials for the treatment of metastatic cancers.

Keyword8-oxo-epiberberine Epithelial-mesenchymal Transition Metastasis Tgf-β1
URLView the original
Indexed BySCIE
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000566798000009
Scopus ID2-s2.0-85089191519
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorZhang,Qingwen; Chen,Xiuping
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macau,China
2.Department of Emergency,Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China
3.Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center,Peking Union Medical College (PUMC),Key Laboratory of Human Disease Comparative Medicine,Ministry of Health,Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases,Beijing,100021,China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Liu,Xin,Zhang,Yiying,ZHOU,Guang Ju,et al. Natural alkaloid 8-oxo-epiberberine inhibited TGF-β1-triggred epithelial-mesenchymal transition by interfering Smad3[J]. Toxicology and Applied Pharmacology,2020,404.
APA Liu,Xin,Zhang,Yiying,ZHOU,Guang Ju,Hou,Ying,Kong,Qi,Lu,Jin Jian,Zhang,Qingwen,&Chen,Xiuping.(2020).Natural alkaloid 8-oxo-epiberberine inhibited TGF-β1-triggred epithelial-mesenchymal transition by interfering Smad3.Toxicology and Applied Pharmacology,404.
MLA Liu,Xin,et al."Natural alkaloid 8-oxo-epiberberine inhibited TGF-β1-triggred epithelial-mesenchymal transition by interfering Smad3".Toxicology and Applied Pharmacology 404(2020).
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