Curcumin Inhibits TGF-β1-Induced MMP-9 and Invasion through ERK and Smad Signaling in Breast Cancer MDA-MB-231 Cells

Objective: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1, with or without curcumin (<= 10 mu M), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-beta 1-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 mu M) did not show any obvious toxicity to the cells, while 0 similar to 10 mu mol/L caused a concentration-dependent reduction in cell invasion provoked by TGF-beta 1. Curcumin also markedly inhibited TGF-beta 1-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. Conclusion: Curcumin inhibited TGF-beta 1-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-beta/Smad and TGF-beta/ERK signaling.