Lung cancer is one of the most common
malignancies in the world and its
metastasis is the major cause of death in
cancer patients.
Acacetin (5,7-dihydroxy-4'-methoxyflavone), a
flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of
acacetin on invasion and migration in human NSCLC A549 cells was investigated. First, the result demonstrated
acacetin could exhibit an inhibitory effect on the abilities of the adhesion, morphology/actin cytoskeleton arrangement, invasion, and migration by cell-matrix adhesion assay, immunofluorescence assay, Boyden chamber assay, and wound-healing assay. Molecular data showed that the effect of
acacetin in A549 cells might be mediated via sustained inactivation of the phosphorylation of mixed-lineage
protein kinase 3 (MLK3),
mitogen-activated protein kinase kinases 3/6 (MKK3/6), and p38α MAPK signal involved in the downregulation of the expressions of
matrix metalloproteinase-2 (MMP-2),
matrix metalloproteinase-9 (MMP-9), and
urokinase-type plasminogen activator (
u-PA). Next,
acacetin significantly decreased in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), and the nuclear levels of
nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Also, the treatment with
acacetin to A549 cells also leads to a concentration-dependent inhibition on the binding abilities of NF-κB and
activator protein-1 (AP-1). Furthermore, the treatment of specific inhibitor for
p38 MAPK (
SB203580) to A549 cells could cause reduced activities of
MMP-2/9 and
u-PA. In addition,
acacetin significantly decreased the levels of phospho-p38α MAPK,
MMP-2/9, and
u-PA in p38α-cDNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. Our results revealed the anti-migration and anti-invasion effects of
acacetin, which may act as a promising therapeutic agent for the treatment of
lung cancer.