Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-jun and NF-kappaB in human prostate carcinoma DU-145 cells.
BACKGROUND
Matrix metalloproteinases (MMPs) are involved in tumor progression including the carcinoma of the prostate (CaP). Therefore, the effect of (-)-epigallocatechin-3-gallate (EGCG) was determined on the synthesis and activation of tumor invasion-specific MMP-2 and MMP-9 in human prostate carcinoma DU-145 cells.


METHODS
MMP-2 and MMP-9 were determined by zymography and Western blot analysis. Since fibroblast conditioned medium (FCM) partially mimics in vivo tumor-host microenvironment, DU145 cells were co-cultured in FCM.


RESULTS
Treatment of EGCG to DU-145 cells resulted in dose-dependent inhibition of FCM-induced pro and active both forms of MMP-2 and MMP-9 concomitant with marked inhibition of phosphorylation of ERK1/2 and p38. In identical conditions, treatment of EGCG or inhibitors of MEK or p38 to DU-145 cells inhibited FCM-induced phosphorylation of ERK1/2 and/or p38 concomitant reduction in MMP-2 and -9. EGCG also inhibited androgen-induced pro-MMP-2 expression in LNCaP cells. Further, treatment of EGCG also resulted in inhibition of activation of c-jun and NF-kappaB in in vitro DU-145 cells.


CONCLUSIONS
The inhibition of MMP-2 and MMP-9 in DU145 cells by EGCG is mediated via inhibition of phosphorylation of ERK1/2 and p38 pathways, and inhibition of activation of transcription factors c-jun and NF-kappaB. EGCG may play a role in prevention of invasive metastatic processes of both androgen-dependent and -independent prostate carcinoma.
Vayalil
Praveen K
PK
Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Katiyar
Santosh K
SK
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D016758:Genes, jun / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology*
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D002392:Catechin; C045651:epigallocatechin gallate; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9