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

Objective: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion abilityinduced 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 ofcurcumin. After treatment with 10 ng/ml TGF-β1, with or without curcumin (≤10 μM), cell invasion was checkedby 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 byWestern blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Followingtreatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Westernblotting and zymography were employed to examine MMP-9 expression and activity, respectively.
Results: Lowdose 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-regulatedMMP-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 inhibitedTGF-β1-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-β/Smad and TGF-β /ERK signaling.