Regulation of urokinase plasminogen activator by epigallocatechin-3-gallate in human fibrosarcoma cells.
(-)-Epigallocatechin-3-gallate (EGCG), a main flavanol of green tea, potently suppressed the urokinase-type plasminogen activator (uPA) expression in human fibrosarcoma HT 1080 cells. EGCG induced not only the suppression of the uPA promoter activity but also the destabilization of uPA mRNA. EGCG inhibited the phosphorylation of extracellular signal-regulated kinases 1 and 2 (Erk-1/2) and P38 mitogen-activated protein kinase (MAPK), but not the phosphorylation of c-jun N-terminal kinase (JNK) and Akt. Specific inhibitors of Erk-1/2 (2'-amino-3'-methoxyflavone, PD98059) and P38 MAPK (pyridinylimidazole, SB203580) were found to suppress the uPA expression and the uPA promoter activity. However, the specific inhibitors did not affect the uPA mRNA stability. These results suggest that EGCG could regulate the uPA expression by at least two different mechanisms: EGCG may inhibit the Erk-1/2 and P38 MAPK, leading to suppression of the uPA promoter activity, and EGCG may destabilize the uPA mRNA in an Erk-1/2- and p38 MAPK-independent way.
Kim
Mi H
MH
Research Institute of Medical Sciences, Chonnam National University Medical School, 5 Hakdong, Kwangju 501-190, South Korea.
Jung
Min A
MA
Hwang
Young S
YS
Jeong
Min
M
Kim
Seok M
SM
Ahn
Sung J
SJ
Shin
Boo A
BA
Ahn
Bong W
BW
Jung
Young D
YD
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D012333:RNA, Messenger; D002392:Catechin; C045651:epigallocatechin gallate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D015500:Chloramphenicol O-Acetyltransferase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator