title: Curcumin inhibits TGF-β1-induced MMP-9 and invasion through ERK and Smad signaling in breast cancer MDA- MB-231 cells.
abstract: OBJECTIVE
  To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-β1 (TGF-β1) in MDA-MB-231 cells and potential mechanisms.
  
  
  METHODS
  Human breast cancer MDA- MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-β1, with or without curcumin (≤10 μM), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-β1-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively.
  
  
  RESULTS
  Low dose curcumin (≤10 μM) did not show any obvious toxicity to the cells, while 0~10 μmol/L caused a concentration-dependent reduction in cell invasion provoked by TGF-β1. Curcumin also markedly inhibited TGF-β1-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression.
  
  
  CONCLUSIONS
  Curcumin inhibited TGF-β1-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-β/Smad and TGF-β/ERK signaling.
authors: Department of Pathology, Chongqing Medical University, Chongqing, China.
authors: Na
authors: N
authors: Mo
authors: Zheng-Qian
authors: ZQ
authors: Li
authors: Jing
authors: J
authors: Li
authors: You-De
authors: YD
authors: Cao
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D015153:Blotting, Western; D001943:Breast Neoplasms; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D003474:Curcumin