title: Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway.
abstract: BACKGROUND
  The existence of breast cancer stem-like cells (BCSCs) has profound implications for cancer prevention. Genistein, a predominant isoflavone found in soy products, has multiple robust anti-tumor effects in various cancers, especially in the breast and prostate cancer. In this study, we aimed to evaluate genistein inhibition of BCSCs and its potential mechanism by culturing MCF-7 breast cancer cells and implanting these cells into nude mice.
  
  
  METHODS
  Cell counting, colony formation and cell apoptosis analysis were used to evaluate the effect of genistein on breast cancer cells’ growth, proliferation and apoptosis. We then used mammosphere formation assay and CD44CD24 staining to evaluate the effect of genistein on BCSCs in vitro. A nude mice xenograft model was employed to determine whether genistein could target BCSCs in vivo, as assessed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. The potential mechanism was investigated utilizing real-time PCR, western blotting analysis and immunohistochemical staining.
  
  
  RESULTS
  Genistein inhibited the MCF-7 breast cancer cells’ growth and proliferation and promoted apoptosis. Both in vitro and in vivo genistein decreased breast cancer stem cells, and inhibited breast cancer stem-like cells through down-regulation of the Hedgehog-Gli1 Signaling Pathway.
  
  
  CONCLUSIONS
  We demonstrated for the first time that genistein inhibits BCSCs by down-regulating Hedgehog-Gli1 signaling pathway. These findings provide support and rationale for investigating the clinical application of genistein in treating breast cancer, and specifically by targeting breast cancer stem cells.
authors: Panhong
authors: P
authors: Fan
authors: Shujun
authors: S
authors: Fan
authors: Huan
authors: H
authors: Wang
authors: Jun
authors: J
authors: Mao
authors: Yu
authors: Y
authors: Shi
authors: Mohammed M
authors: MM
authors: Ibrahim
authors: Wei
authors: W
authors: Ma
authors: Xiaotang
authors: X
authors: Yu
authors: Zhenhuan
authors: Z
authors: Hou
authors: Bo
authors: B
authors: Wang
authors: Lianhong
authors: L
authors: Li
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014183:Transplantation, Heterologous
chemical_list: D016588:Anticarcinogenic Agents; D053823:Hedgehog Proteins; D019833:Genistein