title: Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells.
abstract: BACKGROUND
  Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models.
  
  
  METHODS
  The in vitro and in vivo effect of genistein in enhancing the response of mCRPC cells to cabazitaxel chemotherapy was evaluated in experimental models.
  
  
  RESULTS
  Genistein increases the expression of pro-apoptotic protein Bax, activates apoptotic signals, and enhances the response to cabazitaxel treatment in mCRPC cells. In a PC3-luciferase xenograft model, the combined treatment with genistein and cabazitaxel significantly retarded the growth of mCRPC when compared to vehicle control, cabazitaxel, or genistein. Tissue staining confirmed the in vivo effect of genistein on the induction of Bax and activation of apoptosis.
  
  
  CONCLUSIONS
  This study provided the first preclinical evidence supporting that genistein could be beneficial in improving cabazitaxel chemotherapy in mCRPC.
authors.affiliation: Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.forename: Shareen
authors.initials: S
authors.lastname: Iqbal
authors.forename: Andrew
authors.initials: A
authors.lastname: Chi
authors.forename: Chad
authors.initials: C
authors.lastname: Ritenour
authors.forename: Yongqiang A
authors.initials: YA
authors.lastname: Wang
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
authors.forename: Daqing
authors.initials: D
authors.lastname: Wu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D043823:Taxoids; D051028:bcl-2-Associated X Protein; C552428:cabazitaxel; D019833:Genistein
keywords: cabazitaxel; chemoresistance; experimental model; genistein; prostate cancer