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Mol Pharmacol. 2009 Jan;75(1):151-7. doi: 10.1124/mol.108.049502. Epub 2008 Oct 3.

Vanillin inhibits matrix metalloproteinase-9 expression through down-regulation of nuclear factor-kappaB signaling pathway in human hepatocellular carcinoma cells.

Author information

1
Department of Radiation Therapy and Oncology, China Medical University Hospital, Taichung, Taiwan.

Abstract

Vanillin has been reported to exhibit anti-invasive and antimetastatic activities by suppressing the enzymatic activity of matrix metalloproteinase-9 (MMP-9). However, the underlying mechanism of anti-invasive activity remains unclear so far. Herein we demonstrate that vanillin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 gelatinolytic activity and suppressed cell invasion through the down-regulation of MMP-9 gene transcription in HepG2 cells. Vanillin significantly reduced the 6.6-fold invasive capacity of HepG2 cells in noncytotoxic concentrations, and this anti-invasive effect was concentration-dependent in the Matrigel invasion assay. Moreover, vanillin significantly suppressed the TPA-induced enzymatic activity of MMP-9 and decreased the induced mRNA level of MMP-9. Analysis of the transcriptional regulation indicated that vanillin suppressed MMP-9 transcription by inhibiting nuclear factor-kappaB (NF-kappaB) activity. Western blot further confirmed that vanillin inhibited NF-kappaB activity through the inhibition of IkappaB-alpha phosphorylation and degradation. In conclusion, vanillin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-kappaB signaling pathway.

PMID:
18835982
DOI:
10.1124/mol.108.049502
[Indexed for MEDLINE]
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