Invasion of
cancer cell induced by
matrix metalloproteinase-9 (MMP-9) is one of pivotal steps in
cancer metastasis. Herein, we investigated how cell invasion was regulated by
berberine (BBR), an
isoquinoline derivative
alkaloid compound, in MDA-MB-231 human
breast cancer cells. The basal level of MMP-9 activity and expression was dose-dependently increased by
TNF-alpha, while TNF-a-induced MMP-9
gelatinase activity and expression was decreased by BBR. To investigate regulatory mechanism of
TNF-alpha-induced MMP-9 expression, we pretreated cells with
UO126 (
MEK inhibitor),
SB203580 (p38 inhibitor) and
SP600125 (JNK inhibitor), respectively. Interestingly,
TNF-alpha-induced MMP-9 activity and expression was decreased by
UO126 and
SB203580, but not by
SP600125. Therefore, we further examined the effects of BBR on
TNF-alpha-induced
AP-1 DNA binding activity which is a downstream target of ERK and p38. Our data showed that
TNF-alpha-induced
AP-1 DNA binding activity was inhibited by BBR. Finally, we investigated the effect of BBR on
TNF-alpha-induced cell invasion.
TNF-alpha-induced cell invasion was significantly decreased by BBR treatment. Taken together, we suggest that
TNF-alpha-induced MMP-9 expression and cell invasion are decreased by BBR through the suppression of
AP-1 DNA binding activity in MDA-MB-231 human
breast cancer cells.