Brazilein, a bioactive compound isolated from Caesalpinia sappan L., has long been used in oriental folk medicines.
Cancer metastasis is a primary cause of
cancer death. However, the anti-metastatic effects of
brazilein remain elusive. In this study, we found that
brazilein inhibited human
breast cancer MDA-MB-231 cell migration and invasion using wound-healing assay and Boyden chamber assay. The results of Western blot,
gelatin zymography and reversed transcription-PCR analysis showed that
brazilein suppressed
matrix metalloproteinase-2 (MMP-2) expression in a concentration-dependent manner.
Brazilein also decreased the
nuclear protein level of
nuclear factor kappaB (NF-κB).
Brazilein potently suppressed the phosphorylation of
p38 mitogen-activated protein kinase (
p38 MAPK), phosphatidylinositide-3-kinase (PI3K) and Akt, but did not affect phosphorylation of extracellular signal regulating
kinase (ERK)1/2 and
c-Jun N-terminal kinase (JNK). Additionally, treatment of
SB203580 (
p38 MAPK inhibitor) or
wortmannin (PI3K inhibitor) resulted in a reduced activity and expression of MMP-2 as well as inhibition on cell migration and invasion in MDA-MB-231 cells. Taken together, these results suggest that
brazilein inhibition of MDA-MB-231 cells may be mediated through inactivation of both PI3K/Akt and
p38 MAPK signaling pathways, leading to inhibitory effect on NF-κB activation. Consequently,
brazilein suppresses MMP-2 expression, and thus confers anti-migration and anti-invasion of MDA-MB-231 cells.