Suppression of PMA-induced tumor cell invasion by capillarisin via the inhibition of NF-kappaB-dependent MMP-9 expression.
Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of capillarisin, a bioactive flavonoid of Artemisia capillaries, on phorbol myristate acetate (PMA)-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Capillarisin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7 and the Matrigel invasion assay showed that capillarisin reduces PMA-induced invasion of MCF-7 cells. Capillarisin has been found to suppress PMA-induced MMP-9 expression through inhibition of the NF-kappaB-dependent transcriptional activity of MMP-9 gene via p38 MAPK and JNK signaling pathways. However, capillarisin had no effect on enzymatic activity of MMP-9 and expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2, the major endogenous inhibitors of MMPs. These results suggest that capillarisin represents a potential anti-metastatic agent suppressing cancer cell invasion through specific inhibition of NF-kappaB-dependent MMP-9 gene expression.
Lee
Syng-Ook
SO
Department of Food Science and Technology, The Center for Traditional Microorganism Resources (TMR), Keimyung University, 1000 Sindang-Dong, Dalseo-Gu, Daegu 704-701, Republic of Korea.
Jeong
Yun-Jeong
YJ
Kim
Mihyun
M
Kim
Cheorl-Ho
CH
Lee
In-Seon
IS
D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002867:Chromones; D004338:Drug Combinations; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D011509:Proteoglycans; D018808:Transcription Factor AP-1; C059485:matrigel; C011185:capillarisin; D003094:Collagen; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate