Tanshinones from Chinese medicinal herb Danshen (Salvia miltiorrhiza Bunge) suppress prostate cancer growth and androgen receptor signaling

Pharm Res. 2012 Jun;29(6):1595-608. doi: 10.1007/s11095-012-0670-3. Epub 2012 Jan 27.

Abstract

Purpose: 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.

Conclusion: AR targeting action of tanshinones was distinct from Casodex and contributed to prostate cancer growth suppression in vitro and in vivo.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / isolation & purification
  • Abietanes / pharmacology*
  • Active Transport, Cell Nucleus
  • Androgen Antagonists / pharmacology
  • Anilides / pharmacology
  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nitriles / pharmacology
  • Phenanthrenes / isolation & purification
  • Phenanthrenes / pharmacology*
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proteasome Endopeptidase Complex / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Androgen / drug effects*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Salvia miltiorrhiza* / chemistry
  • Signal Transduction / drug effects*
  • Time Factors
  • Tosyl Compounds / pharmacology
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • AR protein, human
  • Abietanes
  • Androgen Antagonists
  • Anilides
  • Antineoplastic Agents, Hormonal
  • Antineoplastic Agents, Phytogenic
  • Drugs, Chinese Herbal
  • Nitriles
  • Phenanthrenes
  • RNA, Messenger
  • Receptors, Androgen
  • Tosyl Compounds
  • tanshinone
  • cryptotanshinone
  • bicalutamide
  • Prostate-Specific Antigen
  • Proteasome Endopeptidase Complex