Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma

Clin Cancer Res. 2005 May 15;11(10):3905-14. doi: 10.1158/1078-0432.CCR-04-1974.

Abstract

Purpose: Botanical preparations are widely used by patients with prostate cancer. Scutellaria baicalensis, a botanical with a long history of medicinal use in China, was a constituent of the herbal mixture PC-SPES, a product that inhibited prostate cancer growth in both laboratory and clinical studies. Due to the difficulties encountered when evaluating the efficacy of complex natural products, we sought to identify active chemical constituents within Scutellaria and determine their mechanisms of action.

Experimental design and results: We used high-performance liquid chromatography to fractionate S. baicalensis and identified four compounds capable of inhibiting prostate cancer cell proliferation; baicalein, wogonin, neobaicalein, and skullcapflavone. Comparisons of the cellular effects induced by the entire extract versus the four-compound combination produced comparable cell cycle changes, levels of growth inhibition, and global gene expression profiles (r(2) = 0.79). Individual compounds exhibited antiandrogenic activities with reduced expression of the androgen receptor and androgen-regulated genes. In vivo, baicalein (20 mg/kg/d p.o.) reduced the growth of prostate cancer xenografts in nude mice by 55% at 2 weeks compared with placebo and delayed the average time for tumors to achieve a volume of approximately 1,000 mm(3) from 16 to 47 days (P < 0.001).

Conclusions: Most of the anticancer activities of S. baicalensis can be recapitulated with four purified constituents that function in part through inhibition of the androgen receptor signaling pathway. We conclude that clinical studies evaluating the efficacy of these agents in the context of chemoprevention or the treatment of prostate cancer are warranted.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma / pathology*
  • Cell Cycle / drug effects
  • Cell Proliferation
  • Chromatography, High Pressure Liquid
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Plant Extracts / analysis
  • Plant Extracts / pharmacology*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / veterinary
  • Receptors, Androgen / drug effects*
  • Receptors, Androgen / physiology
  • Scutellaria baicalensis / chemistry*
  • Signal Transduction
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Plant Extracts
  • Receptors, Androgen