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

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.