title: Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways.
abstract: Quercetin, a principal flavanoid compound in onions, has been shown to possess a wide spectrum of pharmacological properties, including anticancer activities. Our earlier study showed that quercetin induced cytotoxic effects on SAS human oral cancer cells. In this study, we found that quercetin significantly reduced wound closure of SAS cells in culture plates after 12- and 24-h treatments. Results indicated that quercetin inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, as measured by western blotting and gelatin zymography. The results from western blotting also showed that quercetin reduced the protein levels of MMP-2, -7, -9 and -10, vascular endothelial growth factor (VEGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, inductible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), urokinase-type plasminogen activator (uPA), phosphatidylinositide-3 kinases (PI3K), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IKBα), IKB-α/β, phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor kinase, alpha/beta (p-IKKα/β), focal adhesion kinase (FAK), son of sevenless homolog-1 (SOS1), growth factor receptor-bound protein-2 (GRB2), mitogen-activated protein kinase kinase kinase-3 (MEKK3), MEKK7, extracellular-signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase 1/2 (JNK1/2), p38, p-p38, Jun proto-oncogene (c-JUN) and p-c-JUN but it did not affect Ras homolog gene family, member A (RhoA), Protein kinase C (PKC) and rat sarcoma viral oncogene homolog (RAS) in SAS cells. Confocal laser microscopy also showed that quercetin promoted the expressions of RhoA and Rho-associated, coiled-coil containing protein kinase-1 (ROCK1), but inhibited the expression of NF-κB p65 in SAS cells. It is concluded from these data that inhibition of migration and invasion of SAS cells by quercetin is associated with the down-regulation of PKC and RhoA by blocking MAPK and PI3K/AKT signaling pathways and NF-κB and uPA, resulting in inhibition of MMP-2 and MMP-9 signaling.
authors: China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan, ROC.
authors: Wan-Wen
authors: WW
authors: Lai
authors: Shu-Chun
authors: SC
authors: Hsu
authors: Fu-Shih
authors: FS
authors: Chueh
authors: Ya-Yin
authors: YY
authors: Chen
authors: Jai-Sing
authors: JS
authors: Yang
authors: Jing-Pin
authors: JP
authors: Lin
authors: Jin-Cherng
authors: JC
authors: Lien
authors: Chung-Hung
authors: CH
authors: Tsai
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D000090063:Proto-Oncogene Mas; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D048052:Mitogen-Activated Protein Kinase 3; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000090063:Proto-Oncogene Mas; D011794:Quercetin; C000715470:MAS1 protein, human; C496540:PTGS2 protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human
keywords: MMP-2; MMP-9; NF-κB; Quercetin; SAS human oral cancer cells; invasion; migration