The inhibitory effect of hesperidin on tumor cell invasiveness occurs via suppression of activator protein 1 and nuclear factor-kappaB in human hepatocellular carcinoma cells.

Hesperidin (HES) 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. First, we suggest that the expression of MMP-9 by TPA involves phosphorylation of IKK, p38, and PKC in hepG2. We also demonstrate that hesperidin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibited the secreted and cytosolic MMP-9 forms in HepG2 cells. Hesperidin significantly suppressed the TPA-induced the mRNA level of MMP-9. Hesperidin suppressed MMP-9 transcription by inhibiting nuclear factor-kappaB (NF-kappaB) and Activator protein 1 (AP-1) activity. Hesperidin suppressed TPA-stimulated NF-kappaB translocation into the nucleus through IkappaB inhibitory signaling pathways and also inhibited TPA-induced AP-1 activity by the inhibitory phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) signaling pathways. In conclusion, Hesperidin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-kappaB an AP-1 signaling pathway.

Lee KH ，Yeh MH ，Kao ST ，Hung CM ，Liu CJ ，Huang YY ，Yeh CC ... -  《-》

Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells.

Yeh MH ，Kao ST ，Hung CM ，Liu CJ ，Lee KH ，Yeh CC ... -  《TOXICOLOGY LETTERS》

Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear factor-kappaB and activator protein 1 signaling pathways in human hepatocellular carcinoma cells: Association with the invasive potential.

Hsiang CY ，Wu SL ，Chen JC ，Lo HY ，Li CC ，Chiang SY ，Wu HC ，Ho TY ... -  《TOXICOLOGY LETTERS》

Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor-kappaB.

Huang Q ，Shen HM ，Ong CN 《BIOCHEMICAL PHARMACOLOGY》

Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-kappaB and AP-1.

Weng CJ ，Chau CF ，Hsieh YS ，Yang SF ，Yen GC ... -  《-》