Saw Palmetto Induces Growth Arrest and Apoptosis of Androgen-Dependent Prostate Cancer LNCaP Cells via Inactivation of STAT 3 and Androgen Receptor Signaling

Int J Oncol. 2007 Sep;31(3):593-600.

Abstract

PC-SPES is an eight-herb mixture that has an activity against prostate cancer. Recently, we purified Saw Palmetto (Serenoa repens) from PC-SPES and found that Saw Palmetto induced growth arrest of prostate cancer LNCaP, DU145, and PC3 cells with ED50s of approximately 2.0, 2.6, and 3.3 microl/ml, respectively, as measured by mitochondrial-dependent conversion of the the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Saw Palmetto induced apoptosis of LNCaP cells in a time- and dose-dependent manner as measured by TUNEL assays. Also, Saw Palmetto increased the expression of p21waf1 and p53 protein in LNCaP cells. In addition, we found that Saw Palmetto down-regulated DHT- or IL-6-induced expression of prostate specific antigen in conjunction with down-regulation of the level of androgen receptor in the nucleus as measured by Western blot analysis. Moreover, Saw Palmetto down-regulated the IL-6-induced level of the phosphorylated form of STAT 3 in LNCaP cells. Furthermore, Saw Palmetto inhibited the growth of LNCaP cells present as tumor xenografts in BALB/c nude mice without adverse effect. These results indicate that Saw Palmetto might be useful for the treatment of individuals with prostate cancer.

Publication types

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

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Animals
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Plant Extracts / pharmacology*
  • Prostate-Specific Antigen / biosynthesis
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction

Substances

  • Androgen Antagonists
  • Interleukin-6
  • Plant Extracts
  • Receptors, Androgen
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Prostate-Specific Antigen
  • saw palmetto extract