Recent reports indicated that ROS is closely related with
cancer metastasis. ROS targets major signaling molecules which are known to be involved in migration and invasion of
cancer cells. Here we report that
maclurin, a major phenolic component of
ethanol extracted mulberry twigs, exerts anti-metastatic effect in A549 human
non-small-cell lung cancer cells.
Maclurin suppresses intracellular ROS level in A549 human
non-small-cell lung cancer cells. Also,
maclurin down-regulates Src and ERK, which are well known to be regulated with redox state. Suppressed Src/FAK and ERK signalings activate GSK3-β, thus inhibiting nuclear accumulation of β-
catenin. As a result, transcriptional expressions of two major
gelatinases (MMP-2 and MMP-9) were significantly down-regulated. Consequently, migration and invasion of A549 human
non-small-cell lung cancer cells were attenuated. Anti-metastatic effect of
maclurin on A549 human
non-small-cell lung cancer cells were diminished by the treatment of
hydrogen peroxide, thus further implicating that the effect of
maclurin may be strongly related with its anti-oxidative activity. Thus, our data indicate that the anti-metastatic effect of
maclurin is exerted by anti-oxidative activity and inhibition of Src/FAK-ERK-β-
catenin signaling pathway.