Suppression of tumor cell invasiveness by hydrolyzable tannins (plant polyphenols) via the inhibition of matrix metalloproteinase-2/-9 activity.
Elevated expression of matrix metalloproteinases (MMPs), especially that of MMP-2 and MMP-9, is associated with increased metastatic potential in many tumor cells. Recently, green tea polyphenol epigallocatechin-3-O-gallate (EGCG) has been shown to inhibit the MMP-2/-9 activity as well as the invasiveness of tumor cells. In this study, we have examined the inhibitory effect of hydrolyzable tannins (plant polyphenols) on the tumor cell invasion. Our results demonstrate that beta-d-glucose whose hydroxy groups are substituted entirely with galloyl group and further some of them are cross-linked to form hexahydroxydiphenoyl group, for example, suppresses the invasiveness of tumor cells much more potently than EGCG via direct inhibition of the MMP-2/-9 activity. Among those examined, 1,2,4-tri-O-galloyl-3,6-hexahydroxydiphenoyl-beta-d-glucose (punicafolin) inhibits the invasion of HT1080 fibrosarcoma cells most potently. These hydrolyzable tannins would provide new leads for the development of potent inhibitors against tumor metastasis.
Tanimura
Susumu
S
Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan.
Kadomoto
Ryoji
R
Tanaka
Takashi
T
Zhang
Ying-Jun
YJ
Kouno
Isao
I
Kohno
Michiaki
M
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D004285:Dogs; D004338:Drug Combinations; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007797:Laminin; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D011509:Proteoglycans; D013634:Tannins / Q000494:pharmacology*; D013662:Tea
C501662:1,2,4-tri-O-galloyl-3,6-hexahydroxydiphenoylglucose; D004338:Drug Combinations; D047348:Hydrolyzable Tannins; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D013634:Tannins; D013662:Tea; C059485:matrigel; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9