Anti-metastatic activities of all-trans retinoic acid, indole-3-carbinol and (+)-catechin in Dunning rat invasive prostate adenocarcinoma cells

Anticancer Res. 2002 Nov-Dec;22(6C):4129-35.

Abstract

Dunning rat invasive prostate adenocarcinoma cells were employed to investigate the anti-metastatic potential and probable mechanisms of action of all-trans retinoic acid (ATRA), indole-3-carbinol (13C) and (+)-catechin (CAT). The invasive parameters studied include: matrigel membrane invasion; zymography and Northern analysis for matrix metalloproteinases (MMPs) activity and gene expression; and Western analysis for the membrane-associated proteins alpha-, beta- and gamma-catenins. ATRA significantly and dose-dependently inhibited matrigel membrane invasion of the cells by 53%, inhibited MMP-2 activity by 71%, MMP-9(80%), alpha-(59%) and beta-(65%) catenin expression at 10 microM (p < 0.01). gamma-Catenin expression was completely inhibited by ATRA even at 2 microM. Catechin at 25 microM decreased matrigel membrane invasion by 24% and also inhibited gamma-catenin protein levels by 58% (p < 0.01). Loss of E-cadherin was implicated in the exacerbation of the anti-metastatic effects of ATRA and CAT by the use of E-cadherin-positive, non-invasive cells. In conclusion, ATRA and CAT show anti-metastatic potential in the invasive rat prostate adenocarcinoma model and gamma-catenin appears to play a mechanistic role.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / secondary
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Cadherins / biosynthesis
  • Catechin / pharmacology*
  • Cell Movement / drug effects
  • Collagen
  • Collagenases / biosynthesis
  • Collagenases / genetics
  • Drug Combinations
  • Indoles / pharmacology*
  • Laminin
  • Male
  • Matrix Metalloproteinase 11
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / genetics
  • Neoplasm Invasiveness
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology
  • Proteoglycans
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cadherins
  • Drug Combinations
  • Indoles
  • Laminin
  • Matrix Metalloproteinase Inhibitors
  • Proteoglycans
  • RNA, Messenger
  • matrigel
  • Tretinoin
  • Catechin
  • Collagen
  • indole-3-carbinol
  • Collagenases
  • Matrix Metalloproteinase 11
  • Metalloendopeptidases
  • collagenase 1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9