title: Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth             by inhibiting NF-κB activity via the Notch-1 pathway.
abstract: Genistein (Gen) has been reported as a protective factor against breast cancer. However, the molecular mechanism by which Gen elicits its effects on triple-negative breast cancer cells has not been fully elucidated. In our study, the breast cancer cell line MDA-MB-231 was selected to determine the action of Gen on triple-negative breast cancer cells. MTT assay, flow cytometric analysis, siRNA transfection, western blotting and nuclear factor-κB (NF-κB) activation-nuclear translocation assay were used to address the role of NF-κB activity and the Notch-1 signaling pathway on the effects of Gen. Our study revealed that Gen elicited a dramatic effect on cell growth inhibition, in a dose-dependent and time-dependent manner. Treatment of MDA-MB-231 cells with 0, 5, 10 or 20 µM Gen induced apoptosis of 6.78, 18.98, 30.45 and 60.64%, respectively. Exposure of MDA-MB-231 cells to Gen also resulted in G2/M phase accumulation of cells corresponding to 4.93, 12.54, 18.93 and 30.95%, respectively. Furthermore, our data demonstrated for the first time that Gen inhibited the growth of MDA-MB-231 triple-negative breast cancer cells by inhibiting NF-κB activity via the Nocth-1 signaling pathway in a dose-dependent manner. We also found that Gen downregulated the expression of cyclin B1, Bcl-2 and Bcl-xL, possibly mediated by NF-κB activation via the Notch-1 signaling pathway. In conclusion, our results suggest that inhibition of NF-κB activity via the Notch-1 pathway may be a novel mechanism by which Gen suppresses the growth of triple-negative breast cancer cells. Further preclinical and clinical studies are warranted to further investigate the application of Gen for the treatment of triple-negative breast cancer.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of                     Nanjing Medical University, 210029 Nanjing, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Lijun
authors.initials: L
authors.lastname: Ling
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zha
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D051881:Receptor, Notch1; D019833:Genistein