title: Aromatic-turmerone attenuates invasion and expression of MMP-9 and COX-2 through inhibition of NF-κB activation in TPA-induced breast cancer cells.
abstract: Recent evidence suggests that breast cancer is one of the most common forms of malignancy in females, and metastasis from the primary cancer site is the main cause of death. Aromatic (ar)-turmerone is present in Curcuma longa and is a common remedy and food. In the present study, we investigated the inhibitory effects of ar-turmerone on expression and enzymatic activity levels of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase (MMP)-9 and cyclooxygenaase-2 (COX-2) in breast cancer cells. Our data indicated that ar-turmerone treatment significantly inhibited enzymatic activity and expression of MMP-9 and COX-2 at non-cytotoxic concentrations. However, the expression of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, MMP-2, and COX-1 did not change upon ar-turmerone treatment. We found that ar-turmerone inhibited the activation of NF-κB, whereas it did not affect AP-1 activation. Moreover, The ChIP assay revealed that in vivo binding activities of NF-κB to the MMP-9 and COX-2 promoter were significantly inhibited by ar-turmerone. Our data showed that ar-turmerone reduced the phosphorylation of PI3K/Akt and ERK1/2 signaling, whereas it did not affect phosphorylation of JNK or p38 MAPK. Thus, transfection of breast cancer cells with PI3K/Akt and ERK1/2 siRNAs significantly decreased TPA-induced MMP-9 and COX-2 expression. These results suggest that ar-turmerone suppressed the TPA-induced up-regulation of MMP-9 and COX-2 expression by blocking NF-κB, PI3K/Akt, and ERK1/2 signaling in human breast cancer cells. Furthermore, ar-turmerone significantly inhibited TPA-induced invasion, migration, and colony formation in human breast cancer cells.
authors: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea.
authors: Sun Young
authors: SY
authors: Park
authors: Young Hun
authors: YH
authors: Kim
authors: YoungHee
authors: Y
authors: Kim
authors: Sang-Joon
authors: SJ
authors: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival; D047369:Chromatin Immunoprecipitation; D030024:Curcuma / Q000737:chemistry; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D012717:Sesquiterpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects / Q000031:analogs & derivatives; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D000972:Antineoplastic Agents, Phytogenic; D016861:Cyclooxygenase Inhibitors; D007659:Ketones; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D034741:RNA, Small Interfering; D012717:Sesquiterpenes; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C078098:ar-turmerone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate