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Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells.

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-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.
AuthorsSangmin Kim, Jae Hyuck Choi, Jong Bin Kim, Seok Jin Nam, Jung-Hyun Yang, Jung-Han Kim, Jeong Eon Lee
JournalMolecules (Basel, Switzerland) (Molecules) Vol. 13 Issue 12 Pg. 2975-85 (Dec 03 2008) ISSN: 1420-3049 [Electronic] Switzerland
PMID19052522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Protein Kinase Inhibitors
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Berberine
  • Matrix Metalloproteinase 9
Topics
  • Berberine (pharmacology)
  • Breast Neoplasms (enzymology, metabolism, pathology)
  • Cell Line, Tumor
  • Enzyme Induction
  • Humans
  • Matrix Metalloproteinase 9 (biosynthesis)
  • Protein Kinase Inhibitors (pharmacology)
  • Transcription Factor AP-1 (metabolism)
  • Tumor Necrosis Factor-alpha (pharmacology)

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