Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo

Carcinogenesis. 2004 Jan;25(1):83-90. doi: 10.1093/carcin/bgg178. Epub 2003 Sep 26.

Abstract

Sulforaphane (SFN), a constituent of cruciferous vegetables, is highly effective in affording protection against chemically induced cancers in animal models. Here, we report that SFN inhibited proliferation of cultured PC-3 human prostate cancer cells by inducing apoptosis that was characterized by appearance of cells with sub-G0/G1 DNA content, formation of cytoplasmic histone associated DNA fragments and cleavage of poly(ADP-ribose)polymerase (PARP). SFN-induced apoptosis was associated with up-regulation of Bax, down-regulation of Bcl-2 and activation of caspases-3, -9 and -8. SFN-induced apoptosis, and cleavage of procaspase-3 and PARP were blocked upon pre-treatment of cells with pan caspase inhibitor z-VADfmk, and specific inhibitors of caspase-9 (z-LEHDfmk) and caspase-8 (z-IETDfmk) suggesting involvement of both caspase-9 and caspase-8 pathways in SFN-induced cell death. Oral administration of SFN (5.6 micro mol, 3 times/week) significantly inhibited growth of PC-3 xenografts in nude mice. For instance, 10 days after starting therapy, the average tumor volumes in control and SFN-treated mice were 170 +/- 13 and 80 +/- 14 mm3, respectively, reflecting a >50% reduction in tumor volume due to SFN administration. To the best of our knowledge, the present study is the first published report to document in vivo anticancer activity of SFN in a tumor xenograft model.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / physiology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Female
  • Humans
  • Isothiocyanates
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / prevention & control*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Thiocyanates / pharmacology*
  • Transplantation, Heterologous
  • bcl-2-Associated X Protein

Substances

  • Anticarcinogenic Agents
  • BAX protein, human
  • Bax protein, mouse
  • Isothiocyanates
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Thiocyanates
  • bcl-2-Associated X Protein
  • Caspases
  • sulforafan