title: Tanshinones from Chinese medicinal herb Danshen (Salvia miltiorrhiza Bunge) suppress prostate cancer growth and androgen receptor signaling.
abstract: OBJECTIVE
  To test whether tanshinones inhibit prostate cancer (PCa) growth at least in part through inhibiting androgen receptor (AR) signaling.
  
  
  METHODS
  We evaluated cell growth, survival and AR signaling parameters of PCa cells after exposure to tanshinones in in vitro models. We also tested the in vivo inhibitory efficacy of tanshinone IIA (TIIA) against LNCaP xenograft model in athymic nude mice.
  
  
  RESULTS
  For androgen-dependent LNCaP cells, a colony growth assay showed strong inhibitory potency following the order of TIIA≈cryptotanshinone>tanshinone I, being 10-30 folds higher than Casodex (racemic). TIIA inhibited growth of LNCaP cells more than several androgen-independent PCa cell lines. All 3 tested tanshinones were devoid of AR agonist activity under castrate condition. Mechanistically, tanshinones inhibited AR nuclear translocation within 2 h, decreased protein and mRNA abundance of AR and its target prostate-specific antigen within 12 h, and stimulated proteosomal degradation of AR. Oral administration of TIIA (25 mg/kg, once daily) retarded LNCaP xenograft growth and down-regulated tumor AR abundance in athymic nude mice.
  
  
  CONCLUSIONS
  AR targeting action of tanshinones was distinct from Casodex and contributed to prostate cancer growth suppression in vitro and in vivo.
authors.affiliation: Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, Minnesota 55912, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Suk-Hyun
authors.initials: SH
authors.lastname: Won
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Jinhui
authors.initials: J
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lü
mesh_terms: D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology*; D021581:Active Transport, Cell Nucleus; D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009570:Nitriles / Q000494:pharmacology; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014105:Tosyl Compounds / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C410798:AR protein, human; D045784:Abietanes; D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D009570:Nitriles; D010616:Phenanthrenes; D012333:RNA, Messenger; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C021751:tanshinone; C037886:cryptotanshinone; C053541:bicalutamide; D017430:Prostate-Specific Antigen; D046988:Proteasome Endopeptidase Complex