title: Methylselenocysteine preventing castration-resistant progression of prostate cancer.
abstract: BACKGROUND
  Castration-resistant progression of prostate cancer after androgen deprivation therapy remains a critical challenge in the clinical management of prostate cancer. Resurgent androgen receptor activity is an established driver of castration-resistant progression, and upregulation of androgen receptor expression has been implicated to contribute to the resurgent androgen receptor activity. We reported previously that methylselenocysteine can decrease the expression and activity of androgen receptor. Here we investigated the ability of methylselenocysteine to inhibit castration-resistant progression of prostate cancer.
  
  
  METHODS
  The regrowth of LNCaP prostate cancer xenografts after castration was monitored. The levels of prostate-specific antigen in mouse serum were measured by ELISA. Tumor cell proliferation and apoptosis were analyzed via Ki-67 immunohistochemistry and TUNEL assay, respectively. Intratumoral angiogenesis was assessed by immunohistochemistry staining of vascular endothelial growth factor and CD31.
  
  
  RESULTS
  We showed that methylselenocysteine delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen deprivation. This was accompanied by decreased serum levels of prostate-specific antigen, inhibition of prostate cancer cell proliferation and tumor angiogenesis, as well as downregulation of androgen receptor and induction of apoptosis in the relapsed tumors.
  
  
  CONCLUSIONS
  The present study represents the first to show the preclinical efficacy of methylselenocysteine in delaying castration-resistant progression of prostate cancer. The findings provide a rationale for evaluating the clinical application of combining methylselenocysteine with androgen deprivation therapy for the treatment of advanced prostate cancer.
authors.affiliation: Basic Medical College, Beihua University, Jilin, China; College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Liu
authors.forename: Xichun
authors.initials: X
authors.lastname: Liu
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Guo
authors.forename: Zuowen
authors.initials: Z
authors.lastname: Liang
authors.forename: Yong
authors.initials: Y
authors.lastname: Tian
authors.forename: Lili
authors.initials: L
authors.lastname: Lu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Xuejian
authors.initials: X
authors.lastname: Zhao
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000473:pathology* / Q000517:prevention & control*; D011897:Random Allocation; D011944:Receptors, Androgen / Q000378:metabolism*; D017279:Selenocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D017279:Selenocysteine; D017430:Prostate-Specific Antigen; C002979:selenomethylselenocysteine
keywords: castration resistance; methylselenocysteine; prostate cancer