Nobiletin, a citrus flavonoid, down-regulates matrix metalloproteinase-7 (matrilysin) expression in HT-29 human colorectal cancer cells.
Overexpression of matrix metalloproteinases (MMPs) is associated with cancer metastasis. We assessed mRNA expression of MMPs in six human colorectal cancer cell lines and found a considerable level of MMP-7 expression in HT-29 cells. Next, we searched for natural and synthetic compounds that cause a reduction in the production of proMMP-7 protein, and found that nobiletin (NOB), quercetin, valeryl salicylate, and sulindac sulfone demonstrated marked inhibition. Importantly, NOB attenuated proMMP-7 protein and its mRNA expression both concentration- and time-dependently via a reduction of activator protein-1 (AP-1) DNA binding activity, suggesting it as a promising agent for suppression of cancer cell invasion and metastasis through MMP-7 gene repression.
Kawabata
Kyuichi
K
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan.
Murakami
Akira
A
Ohigashi
Hajime
H
D015179:Colorectal Neoplasms / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D047309:Flavones / Q000494:pharmacology*; D020869:Gene Expression Profiling; D019073:HT29 Cells; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D047309:Flavones; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C008661:nobiletin; D020783:Matrix Metalloproteinase 7