title: Estrogen receptor beta-mediated proliferative inhibition and apoptosis in human breast cancer by calycosin and formononetin.
abstract: BACKGROUND
  Calycosin and formononetin are two main components of isoflavones. In our previous studies, we have respectively reported their antitumor activities on breast cancer cell MCF-7. To further investigate the feasibility of isoflavones in clinically treating breast carcinoma, here we specifically focused on the comparison between calycosin and formononetin, along with the relevant mechanism.
  
  
  METHODS
  ER-positive (MCF-7, T-47D) and ER-negative breast cancer cells (MDA-231, MDA-435) were respectively treated with calycosin or formononetin. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry. mRNA levels of ER beta (ERβ) and miR-375 were quantifed by real-time PCR. Expression of ERβ and insulin-like growth factor 1 receptor (IGF-1R), and activation of poly (ADP-ribose) polymerase 1 (PARP-1) were determined by Western blotting.
  
  
  RESULTS
  Both calycosin and formononetin impaired proliferation and triggered apoptosis of ER-positive breast cancer cells (MCF-7, T-47D) in a time- and dose-dependent manner, especially in the treatment with calycosin. However, no such effect was observed in ER-negative breast cancer cells, indicating the correlation between isoflavones-induced inhibitory effect and ERs. Thus calycosin and most sensitive MCF-7 cells were used to study the relevant signaling pathway. After the treatment of calycosin, ERβ expression was significantly increased in MCF-7 cells, followed by decrease of IGF-1R, activation of PARP-1 cleavage and downregulation of miR-375.
  
  
  CONCLUSIONS
  Calycosin has an advantage on inhibiting breast cancer growth in comparison with formononetin, which is obtained by ERβ-mediated regulation of IGF-1R signaling pathways and miR-375 expression.
authors.affiliation: School of Basic Medical Sciences, Guilin Medical University, Guilin, Guilin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047629:Estrogen Receptor beta; D007529:Isoflavones; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; C007768:formononetin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D017526:Receptor, IGF Type 1