title: Formononetin promotes cell cycle arrest via downregulation of Akt/Cyclin D1/CDK4 in human prostate cancer cells.
abstract: BACKGROUND
  Formononetin is an O-methylated isoflavone isolated from the root of Astragalus membranaceus. It has already been reported that formononetin could inhibit cell proliferation and induce cell apoptosis in several cancers, including prostate cancer. This study aimed to further investigate whether cell cycle arrest is involved in formononetin-mediated antitumor effect in human prostate cancer cells, along with the underlying molecular mechanism.
  
  
  METHODS
  Human prostate cancer cells PC-3 and DU145 were respectively treated with various concentrations of formononetin. The inhibitory effect of formononetin on proliferation of prostate cancer cells was determined using MTT assays and flow cytometry. Next, formononetin-induced alterations in cyclin D1, CDK4 and Akt expression in PC-3 cells were detected by real-time PCR and western blot.
  
  
  RESULTS
  Formononetin dose-dependently inhibited prostate cancer cell proliferation via the induction of cell cycle arrest at G0/G1 phase in vitro, which was more evident in PC-3 cells. Meanwhile, concomitant with reduced phosphorylation of Akt in PC-3 cells, formononetin remarkably downregulated expression levels of cyclin D1 and CDK4 in a dose-dependent manner. More interestingly, in the in vivo studies, formononetin showed a noticeable inhibition of tumor growth in recipient mice.
  
  
  CONCLUSIONS
  Formononetin could exhibit inhibitory activity against human prostate cancer cells in vivo and in vitro, which is associated with G1 cell cycle arrest by inactivation of Akt/cyclin D1/CDK4. Therefore, formononetin may be used as a candidate agent for clinical treatment of prostate cancer in the future.
authors.affiliation: Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Li
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhao
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.forename: Weihua
authors.initials: W
authors.lastname: Huang
authors.forename: Haibiao
authors.initials: H
authors.lastname: Yan
authors.forename: Zhian
authors.initials: Z
authors.lastname: Ling
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects* / Q000235:genetics
chemical_list: D007529:Isoflavones; D019938:Cyclin D1; C007768:formononetin; D051057:Proto-Oncogene Proteins c-akt; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4