dykellic-acid and prolinedithiocarbamate

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.

Topics: Enzyme Induction; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Luciferases; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neoplasm Proteins; NF-kappa B; Proline; Promoter Regions, Genetic; Propionates; Protein Structure, Tertiary; Pyrones; RNA, Messenger; Tetradecanoylphorbol Acetate; Thiocarbamates; Thioctic Acid; Transcription Factor AP-1; Transcriptional Activation; Transfection; Tumor Cells, Cultured