Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells.
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.
Kim
Sangmin
S
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea.
Choi
Jae Hyuck
JH
Kim
Jong Bin
JB
Nam
Seok Jin
SJ
Yang
Jung-Hyun
JH
Kim
Jung-Han
JH
Lee
Jeong Eon
JE
D001599:Berberine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004790:Enzyme Induction; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D020780:Matrix Metalloproteinase 9