We have previously isolated
dieckol, a nutrient
polyphenol compound, from the brown alga, Ecklonia cava (Lee et al.,2010a).
Dieckol shows both antitumor and
antioxidant activity and thus is of special interest for the development of chemopreventive and chemotherapeutic agents against
cancer. However, the mechanism by which
dieckol exerts its antitumor activity is poorly understood. Here, we show that
dieckol, derived from E. cava, inhibits migration and invasion of HT1080 cells by scavenging intracellular
reactive oxygen species (ROS). H2O2 or
integrin signal-mediated ROS generation increases migration and invasion of HT1080 cells, which correlates with Rac1 activation and increased expression and phosphorylation of
focal adhesion kinase (FAK). Rac1 activation is required for ROS generation. Depletion of FAK by
siRNA suppresses Rac1-ROS-induced cell migration and invasion.
Dieckol treatment attenuated intracellular ROS levels and activation of Rac1 as well as expression and phosphorylation of FAK.
Dieckol treatment also decreases complex formation of FAK-Src-p130C as and expression of MMP2, 9, and 13. These results suggest that the Rac1-ROS-linked cascade enhances migration and invasion of HT1080 cells by inducing expression of
MMPs through activation of the FAK signaling pathway, whereas
dieckol downregulates FAK signaling through scavenging intracellular ROS. This finding provides new insights into the mechanisms by which
dieckol is able to suppress human
cancer progresssion and
metastasis. Therefore, we suggest that
dieckol is a potential therapeutic agent for
cancer treatment.