Labda-8(17),12,14-trien-19-oic acid contained in fruits of Cupressus sempervirens suppresses benign prostatic hyperplasia in rat and in vitro human models through inhibition of androgen and STAT-3 signaling

Phytother Res. 2014 Aug;28(8):1196-203. doi: 10.1002/ptr.5114. Epub 2014 Jan 7.


Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5 μM (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ß and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity.

Keywords: BPH; BPH stromal cells; Cupressus; STAT-3; citral; communic acid; diterpene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cupressus / chemistry*
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Fruit / chemistry
  • Humans
  • Male
  • Phosphorylation
  • Prostatic Hyperplasia / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism


  • Androgens
  • Diterpenes
  • STAT3 Transcription Factor
  • labda-8(17),12,14-trien-19-oic acid