TY - JOUR T1 - Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor-κB Signaling Pathway in Human Hepatocellular Carcinoma Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 151 LP - 157 DO - 10.1124/mol.108.049502 VL - 75 IS - 1 AU - Ji-An Liang AU - Shih-Lu Wu AU - Hsin-Yi Lo AU - Chien-Yun Hsiang AU - Tin-Yun Ho Y1 - 2009/01/01 UR - http://molpharm.aspetjournals.org/content/75/1/151.abstract N2 - 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-κB (NF-κB) activity. Western blot further confirmed that vanillin inhibited NF-κB activity through the inhibition of IκB-α phosphorylation and degradation. In conclusion, vanillin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-κB signaling pathway. The American Society for Pharmacology and Experimental Therapeutics ER -