Dykellic acid inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting nuclear factor kappa B transcriptional activity.
Proteolytic degradation of the extracellular matrix and tumor metastasis correlate with expression of endopeptidases known as matrix metalloproteinases (MMPs). Expression of MMPs is regulated by cytokines and signal transduction pathways, including those activated by phorbol myristate acetate. We found that dykellic acid, a fungal metabolite, significantly inhibits the phorbol myristate acetate-induced increase in MMP-9 expression and activity. These effects of dykellic acid are time- and dose-dependent, and correlate with decreased MMP-9 promoter activity and mRNA expression. Whereas this compound does not affect DNA binding activity of nuclear factor kappa B (NF kappa B), dykellic acid does inhibit transactivation of NF kappa B. These data demonstrate a role for NF kappa B in the regulation of MMP-9 expression and the ability of dykellic acid to suppress this action of NF kappa B.
Woo
Ju-Hyung
JH
Department of Immunology, School of Medicine, Keimyung University, Taegu 700-712, Korea.
Park
Jong-Wook
JW
Lee
Sung-Hee
SH
Kim
Young-Ho
YH
Lee
In Kyu
IK
Gabrielson
Edward
E
Lee
Sang-Han
SH
Lee
Ho-Jae
HJ
Kho
Yung-Hee
YH
Kwon
Taeg Kyu
TK
D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011753:Pyrones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D016328:NF-kappa B; D009363:Neoplasm Proteins; D011422:Propionates; D011753:Pyrones; D012333:RNA, Messenger; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; C406051:dykellic acid; C066229:prolinedithiocarbamate; D008063:Thioctic Acid; D011392:Proline; D008156:Luciferases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate