Vanillin inhibits matrix metalloproteinase-9 expression through down-regulation of nuclear factor-kappaB signaling pathway in human hepatocellular carcinoma cells.
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.
Department of Radiation Therapy and Oncology, China Medical University Hospital, Taichung, Taiwan.
Ji-An
JA
Liang
Shih-Lu
SL
Wu
Hsin-Yi
HY
Lo
Chien-Yun
CY
Hsiang
Tin-Yun
TY
Ho
D001547:Benzaldehydes / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005562:Formazans / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts / Q000378:metabolism
D001547:Benzaldehydes; D005562:Formazans; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D013778:Tetrazolium Salts; C079782:MTT formazan; C100058:vanillin; D008156:Luciferases