title: Emodin inhibits breast cancer cell proliferation through the ERα-MAPK/Akt-cyclin D1/Bcl-2 signaling pathway.
abstract: BACKGROUND
  The aim of the present study was to investigate the involvement of emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the estrogen (E2) signal pathway in vitro.
  
  
  METHODS
  MTT assays were used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA-MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the effects of emodin on the expression of estrogen receptor α, cyclin D1 and B-cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess transcriptional activity of ERα.
  
  
  RESULTS
  Emodin could inhibit E2-induced MCF-7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in G0/G1 phase, further blocking the effect of E2 on expression and transcriptional activity of ERα. Moreover, Emodin influenced the ER α genomic pathway via downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non-genomic pathway via decreased PI3K/Akt protein expression.
  
  
  CONCLUSIONS
  These findings indicate that emodin exerts inhibitory effects on MCF-7 cell proliferation via inhibiting both non-genomic and genomic pathways.
authors.affiliation: School of Life Science, Liaoning Normal University, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Dalian, China E-mail : xmj1222@sina.com.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Sui
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Xie
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism*; D004642:Emodin / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: C530104:CCND1 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D004642:Emodin