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Molecules 2008, 13(12), 2975-2985; doi:10.3390/molecules13122975
Article

Berberine Suppresses TNF-α-induced MMP-9 and Cell Invasion through Inhibition of AP-1 Activity in MDA-MB-231 Human Breast Cancer Cells

1, 1, 2, 1, 1, 1,*  and 1,*
1 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea 2 Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, South Korea
* Authors to whom correspondence should be addressed.
Received: 10 November 2008 / Revised: 25 November 2008 / Accepted: 26 November 2008 / Published: 3 December 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.
Keywords: Berberine; AP-1; MMP-9; Cell invasion Berberine; AP-1; MMP-9; Cell invasion
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kim, S.; Choi, J.H.; Kim, J.B.; Nam, S.J.; Yang, J.-H.; Kim, J.-H.; Lee, J.E. Berberine Suppresses TNF-α-induced MMP-9 and Cell Invasion through Inhibition of AP-1 Activity in MDA-MB-231 Human Breast Cancer Cells. Molecules 2008, 13, 2975-2985.

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