berberine suppresses tnf-α-induced mmp-9 and cell invasion through inhibition of ap-1 activity in mda-mb-231 human breast cancer cells
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2008
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Abstract
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-α, while TNF-a-induced MMP-9 gelatinase activity and expression was decreased by BBR. To investigate regulatory mechanism of TNF-α-induced MMP-9 expression, we pretreated cells with UO126 (MEK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor), respectively. Interestingly, TNF-α-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-α-induced AP-1 DNA binding activity which is a downstream target of ERK and p38. Our data showed that TNF-α-induced AP-1 DNA binding activity was inhibited by BBR. Finally, we investigated the effect of BBR on TNF-α-induced cell invasion. TNF-α-induced cell invasion was significantly decreased by BBR treatment. Taken together, we suggest that TNF-α-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.
| Reference Key |
choi2008moleculesberberine
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|---|---|
| Authors | ;Jae Hyuck Choi;Jong Bin Kim;Seok Jin Nam;Jung-Hyun Yang;Jung-Han Kim;Jeong Eon Lee;Sangmin Kim |
| Journal | Journal of ethnopharmacology |
| Year | 2008 |
| DOI |
10.3390/molecules13122975
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| URL | |
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