Berberine Suppresses Fibronectin Expression through Inhibition of c-Jun Phosphorylation in Breast Cancer Cells.
- Author:
Yisun JEONG
1
;
Daeun YOU
;
Hyun Gu KANG
;
Jonghan YU
;
Seok Won KIM
;
Seok Jin NAM
;
Jeong Eon LEE
;
Sangmin KIM
Author Information
- Publication Type:Original Article
- Keywords: Berberine; Cell adhesion; Fibronectins; Transcription factor AP-1
- MeSH: Berberine*; Blotting, Western; Breast Neoplasms*; Breast*; Cell Adhesion; Fibronectins*; Humans; Phosphorylation*; Prognosis; Real-Time Polymerase Chain Reaction; RNA, Messenger; Transcription Factor AP-1; Triple Negative Breast Neoplasms
- From:Journal of Breast Cancer 2018;21(1):21-27
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The exact mechanism regulating fibronectin (FN) expression in breast cancer cells has not been fully elucidated. In this study, we investigated the pharmacological mechanism of berberine (BBR) with respect to FN expression in triple-negative breast cancer (TNBC) cells. METHODS: The clinical significance of FN mRNA expression was analyzed using the Kaplan-Meier plotter database (http://kmplot.com/breast). FN mRNA and protein expression levels were analyzed by real-time polymerase chain reaction and western blotting, respectively. RESULTS: Using publicly available clinical data, we observed that high FN expression was associated with poor prognosis in patients with breast cancer. FN mRNA and protein expression was increased in TNBC cells compared with non-TNBC cells. As expected, recombinant human FN significantly induced cell spreading and adhesion in MDA-MB231 TNBC cells. We also investigated the regulatory mechanism underlying FN expression. Basal levels of FN mRNA and protein expression were downregulated by a specific activator protein-1 (AP-1) inhibitor, SR11302. Interestingly, FN expression in TNBC cells was dose-dependently decreased by BBR treatment. The level of c-Jun phosphorylation was also decreased by BBR treatment. CONCLUSION: Our findings demonstrate that FN expression is regulated via an AP-1–dependent mechanism, and that BBR suppresses FN expression in TNBC cells through inhibition of AP-1 activity.
