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
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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.
Kim S, Choi JH, Kim JB, Nam SJ, Yang J-H, Kim J-H, Lee JE. 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(12):2975-2985.
Kim, Sangmin; Choi, Jae Hyuck; Kim, Jong Bin; Nam, Seok Jin; Yang, Jung-Hyun; Kim, Jung-Han; Lee, Jeong Eon. 2008. "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 13, no. 12: 2975-2985.