Dykellic acid inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting nuclear factor κB transcriptional activity

• Published in: Cancer research (Chicago, Ill.) Ill.), 2003-06, Vol.63 (12), p.3430-3434
• Main Authors: WOO, Ju-Hyung, PARK, Jong-Wook, LEE, Sung-Hee, KIM, Young-Ho, IN KYU LEE, GABRIELSON, Edward, LEE, Sang-Han, LEE, Ho-Jae, KHO, Yung-Hee, TAEG KYU KWON
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Chemotherapy; Enzyme Induction - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Genes, Reporter; Humans; Luciferases - analysis; Luciferases - genetics; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - genetics; Medical sciences; Neoplasm Invasiveness; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; NF-kappa B - antagonists & inhibitors; NF-kappa B - chemistry; NF-kappa B - physiology; Pharmacology. Drug treatments; Proline - analogs & derivatives; Proline - pharmacology; Promoter Regions, Genetic - drug effects; Propionates - pharmacology; Protein Structure, Tertiary; Pyrones - pharmacology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Tetradecanoylphorbol Acetate - antagonists & inhibitors; Tetradecanoylphorbol Acetate - pharmacology; Thiocarbamates - pharmacology; Thioctic Acid - pharmacology; Transcription Factor AP-1 - metabolism; Transcriptional Activation - drug effects; Transfection; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - enzymology
• ISSN: 0008-5472; 1538-7445

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.