Damnacanthal, an
anthraquinone present in noni plants, targets several
tyrosine kinases and has antitumoral effects. This study aims at getting additional insight on the potential of
damnacanthal as a natural antitumor compound. The direct effect of
damnacanthal on c-Met was tested by in vitro activity assays. Additionally, Western blots of c-Met phosphorylation in human
hepatocellular carcinoma Hep G2 cells were performed. The antitumor effects of
damnacanthal were tested by using cell growth, soft
agar clonogenic, migration and invasion assays. Their mechanisms were studied by Western blot, and cell cycle, apoptosis and zymographic assays. Results show that
damnacanthal targets c-Met both in vitro and in cell culture. On the other hand,
damnacanthal also decreases the phosphorylation levels of Akt and targets
matrix metalloproteinase-2 secretion in Hep G2 cells. These molecular effects are accompanied by inhibition of the growth and clonogenic potential of Hep G2
hepatocellular carcinoma cells, as well as induction of Hep G2 apoptosis. Since c-Met has been identified as a new potential therapeutical target for personalized treatment of
hepatocellular carcinoma,
damnacanthal and noni extract supplements containing it could be potentially interesting for the treatment and/or
chemoprevention of
hepatocellular carcinoma through its inhibitory effects on the HGF/c-Met axis.