The prevention and treatment effects of tanshinone IIA on oestrogen/androgen-induced benign prostatic hyperplasia in rats

J Steroid Biochem Mol Biol. 2015 Jan:145:28-37. doi: 10.1016/j.jsbmb.2014.09.026. Epub 2014 Oct 5.

Abstract

Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in elderly men. Tanshinone IIA (Tan IIA) is the active ingredient extracted from the traditional Chinese medicine Salvia, and it has effects of anti-oxidation, anti-inflammation, vascular smooth muscle relaxation and tumour growth inhibition. The present study aimed to investigate the therapeutic potential of Tan IIA in the prevention and treatment of BPH. In a rat model of oestradiol/testosterone-induced BPH, Tan IIA inhibited the increase in the thickness of the peri-glandular smooth muscle layer, suppressed the expression of proliferating cell nuclear antigen (PCNA) in both prostate epithelial cells and stromal cells, downregulated the expression of androgen receptor (AR), oestrogen receptor α (ERα), cyclin B1 (CCNB1) and cyclin D1 (CCND1), and effectively prevented the development of the disorder. In vitro, Tan IIA inhibited the proliferation of human prostate stromal cell line WPMY-1 and epithelial cell line RWPE-1 in a dose- and time-dependent manner. In WPMY-1 cells, Tan IIA treatment arrested the cell cycle at the G2/M phase and downregulated the expression of CCNB1. However, in RWPE-1 cells, Tan IIA treatment arrested cell cycle at the G0/G1 phase and reduced the expression of CCND1. Tan IIA also reduced the expression of ERα and AR in WPMY-1 and RWPE-1 cells. These results suggest that Tan IIA can inhibit the growth of prostate stromal and epithelial cells both in vivo and in vitro by a mechanism that may involve arresting the cell cycle and downregulating ERα and AR expression.

Keywords: Androgen receptor; Benign prostatic hyperplasia; Cyclins; Oestrogen receptor α; Tanshinone IIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / therapeutic use*
  • Androgens / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Apoptosis
  • Cell Cycle
  • Cell Line
  • Cell Proliferation
  • Cyclin B1 / metabolism
  • Cyclin D / metabolism
  • Cyclins / metabolism
  • Epithelial Cells / cytology
  • Estrogen Receptor alpha / metabolism
  • Estrogens / pharmacology*
  • Humans
  • Male
  • Proliferating Cell Nuclear Antigen / metabolism
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostatic Hyperplasia / drug therapy*
  • Rats
  • Rats, Wistar
  • Receptors, Androgen / metabolism

Substances

  • Abietanes
  • Androgens
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclin B1
  • Cyclin D
  • Cyclins
  • Estrogen Receptor alpha
  • Estrogens
  • Proliferating Cell Nuclear Antigen
  • Receptors, Androgen
  • tanshinone