Inhibitory effects of glycoprotein-120 (G-120) from Ulmus davidiana Nakai on cell growth and activation of matrix metalloproteinases.
Excessive breakdown of extracellular matrix by metalloproteinases (MMPs) occurs in many pathological conditions. Consequently, methods for inhibiting MMP activity have therapeutic potential. In this study, we investigated the effect of G-120, a 120 kDa glycoprotein purified from the Oriental herbal plant, Ulmus davidiana Nakai (UDN), on the activity and production of several MMPs by evaluating its growth inhibitory effect on NIH 3T3 cells. Tritium uptake assays showed that proliferation of NIH 3T3 cells was strongly suppressed, and G-120-mediated inhibition of DNA synthesis proved to involve a cytostatic, rather than a cytotoxic, effect, as shown by cytotoxicity and apoptosis assays. More importantly, G-120 strongly reduced the gelatinolytic and collagenase activities of MMP proteins, as well as expression of MMP-2 and MMP-9. Electrophoretic mobility shift assays revealed that it suppressed the DNA binding activity of NF-kappaB. Collectively, our observations show that G-120 strongly inhibits the activation of MMPs and NF-kappaB.
Son
Young-Ok
YO
Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756, Korea.
Lee
Kyung-Yeol
KY
Choi
Ki-Choon
KC
Chung
Youngji
Y
Kim
Jong-Ghee
JG
Jeon
Young-Mi
YM
Jang
Yong-Suk
YS
Lee
Jeong-Chae
JC
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D041681:NIH 3T3 Cells; D010940:Plant Proteins / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D034403:Ulmus / Q000737:chemistry*
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010940:Plant Proteins; D004247:DNA; D020782:Matrix Metalloproteinases