Maclurin suppresses migration and invasion of human non-small-cell lung cancer cells via anti-oxidative activity and inhibition of the Src/FAK-ERK-beta-catenin pathway

Abstract

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-beta, thus inhibiting nuclear accumulation of beta-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-beta-catenin signaling pathway.