title: Biochanin A promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in breast cancer cells.
abstract: BACKGROUND
  Biochanin A and formononetin are O-methylated isoflavones that are isolated from the root of Astragalus membranaceus, and have antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and in vitro studies to further investigate the potential effect of biochanin A in promoting cell proliferation in estrogen receptor (ER)-positive cells, and to elucidate underlying mechanisms.
  
  
  METHODS
  ERα-positive breast cancer cells (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. Compared with the control, low biochanin A concentrations (2-6 μM) stimulated ERα-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells were used to study the relevant signaling pathway.
  
  
  RESULTS
  After treatment with biochanin A, ERα, miR-375, and Bcl-2 expression was significantly upregulated. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with biochanin A increased significantly.
  
  
  CONCLUSIONS
  This study demonstrated that biochanin A promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.
authors.affiliation: School of Basic Medical Sciences, Guilin Medical University, Guilin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Ge
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
authors.forename: Sien
authors.initials: S
authors.lastname: Zeng
authors.forename: Zhaoquan
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics*; D025461:Feedback, Physiological / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
chemical_list: D016588:Anticarcinogenic Agents; C000595707:BCL2 protein, human; D047628:Estrogen Receptor alpha; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D019833:Genistein; C004541:biochanin A