Ontology highlight
ABSTRACT: Background and purpose
Protocatechuic acid (PCA) is plentiful in edible fruits and vegetables and is thus one anti-oxidative component of normal human diets. However, the molecular mechanisms involved in the chemopreventive activity of PCA are poorly understood. Here, we investigated the mechanism(s) underlying the anti-metastatic potential of PCA.Experimental approach
We used AGS cells in a wound healing model and Boyden chamber assays in vitro and injection of B16/F10 melanoma cells in mice (metastasis model in vivo) to analyse the effect of PCA on cancer cell invasion and metastasis. The activities and expression of molecular proteins were measured by zymographic assay, real-time RT-PCR and Western blotting.Key results
PCA inhibited cell migration and invasion at non-cytotoxic concentrations. Decreased expression of matrix metalloproteinase (MMP)-2 and a coincident increase in tissue inhibitor of MMP followed treatment with PCA. The PCA-inhibited MMP-2 activity and expression was accompanied by inactivation of NF-?B. All these effects of PCA could be mediated via the RhoB/ protein kinase C? (PKC?) and Ras/Akt cascade pathways, as demonstrated by inhibition of PKC? and transfection of PKC? siRNA and ras overexpression vector. Finally, PCA inhibited metastasis of B16/F10 melanoma cells to the liver in mice.Conclusion and implications
Our data imply that PCA down-regulated the Ras/Akt/NF-?B pathway by targeting RhoB activation, which in turn led to a reduction of MMP-mediated cellular events in cancer cells and provides a new mechanism for the anti-cancer activity of PCA.
SUBMITTER: Lin HH
PROVIDER: S-EPMC3012419 | biostudies-literature | 2011 Jan
REPOSITORIES: biostudies-literature
British journal of pharmacology 20110101 1
<h4>Background and purpose</h4>Protocatechuic acid (PCA) is plentiful in edible fruits and vegetables and is thus one anti-oxidative component of normal human diets. However, the molecular mechanisms involved in the chemopreventive activity of PCA are poorly understood. Here, we investigated the mechanism(s) underlying the anti-metastatic potential of PCA.<h4>Experimental approach</h4>We used AGS cells in a wound healing model and Boyden chamber assays in vitro and injection of B16/F10 melanoma ...[more]