Ginseng saponin metabolite suppresses phorbol ester-induced matrix metalloproteinase-9 expression through inhibition of activator protein-1 and mitogen-activated protein kinase signaling pathways in human astroglioma cells.
Aberrant expression of matrix metalloproteinase-9 (MMP-9) is implicated in the process of invasion and angiogenesis of malignant tumors as well as in inflammatory diseases of the CNS. Therefore, the development of compounds that can inhibit or suppress MMP-9 is required to treat brain tumors. We investigated the effects of a ginseng saponin metabolite, compound K (20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol), on MMP-9 expression in human astroglioma cells. Compound K significantly inhibited the secretion and protein expression of MMP-9 induced by PMA. The inhibitory effect of compound K on MMP-9 expression correlated with decreased MMP-9 mRNA levels and suppression of MMP-9 promoter activity. The compound K-mediated inhibition of MMP-9 gene expression appears to occur via AP-1 because its DNA-binding and transcriptional activities were suppressed by the agent. Furthermore, compound K significantly repressed the PMA-mediated activation of p38 MAPK, ERK and JNK, which are upstream modulators of AP-1. Finally, compound K inhibited the in vitro invasiveness of glioma cells. Therefore, inhibition of MMP-9 expression by compound K might have therapeutic potential for controlling the growth and invasiveness of brain tumors.
Jung
Soo-Hyun
SH
Department of Neuroscience, Ewha Institute of Neuroscience, College of Medicine, Ewha Woman's University, Seoul, South Korea.
Woo
Moon-Sook
MS
Kim
So-Young
SY
Kim
Won-Ki
WK
Hyun
Jin-Won
JW
Kim
Eun-Jin
EJ
Kim
Dong-Hyun
DH
Kim
Hee-Sun
HS
D001254:Astrocytoma / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D004273:DNA, Neoplasm; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D036145:Ginsenosides; D020780:Matrix Metalloproteinase 9; D018808:Transcription Factor AP-1; C112772:ginsenoside compound K