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.
Nwankwo
Joseph O
JO
Department of Biochemistry, BSB 4403, College of Medicine, University of Iowa, Iowa City, IA 52242, USA. joseph-nwankwo@uiowa.edu
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D002392:Catechin / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics; D004338:Drug Combinations; D007211:Indoles / Q000494:pharmacology*; D007797:Laminin; D008297:Male; D053507:Matrix Metalloproteinase 11; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011509:Proteoglycans; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015820:Cadherins; D004338:Drug Combinations; D007211:Indoles; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D014212:Tretinoin; D002392:Catechin; D003094:Collagen; C016517:indole-3-carbinol; D017364:Collagenases; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases; C417249:collagenase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9