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

Soo Hyun Jung, Moon Sook Woo, So Young Kim, Won-Ki Kim, Jin Won Hyun, Eun Jin Kim, Dong Hyun Kim, Hee Sun Kim

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

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-(β-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.

Original languageEnglish
Pages (from-to)490-497
Number of pages8
JournalInternational Journal of Cancer
Volume118
Issue number2
DOIs
Publication statusPublished - 2006 Jan 15
Externally publishedYes

Fingerprint

Panax
Saponins
Matrix Metalloproteinase 9
Astrocytoma
Transcription Factor AP-1
Phorbol Esters
Mitogen-Activated Protein Kinases
Brain Neoplasms
Central Nervous System Diseases
p38 Mitogen-Activated Protein Kinases
Glioma
ginsenoside M1
Gene Expression
Messenger RNA
DNA

Keywords

  • Activator protein-1
  • Astroglioma
  • Compound K
  • Matrix metalloproteinase-9
  • Mitogen-activated protein kinase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Jung, Soo Hyun; Woo, Moon Sook; Kim, So Young; Kim, Won-Ki; Hyun, Jin Won; Kim, Eun Jin; Kim, Dong Hyun; Kim, Hee Sun.

In: International Journal of Cancer, Vol. 118, No. 2, 15.01.2006, p. 490-497.

Research output: Contribution to journalArticle

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abstract = "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-(β-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.",
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