Curcumin downregulates the expression of Snail via suppressing Smad2 pathway to inhibit TGF-β1-induced epithelial-mesenchymal transitions in hepatoma cells

Hepatocellular carcinoma (HCC) remains the third cause of cancer-related mortality. Resection and transplantation are the only curative treatments available but are greatly hampered by high recurrence rates and development of metastasis, the initiation of cancer metastasis requires migration and invasion of cells, which is enabled by epithelial-mesenchymal transitions (EMT). TGF-beta 1 is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation and apoptosis. TGF-beta 1 is known as a major inducer of EMT, and it was reported that TGF-beta 1 induced EMT via Smad-dependent and Smadindependent pathways. However, the extrinsic signals of TGF-beta 1 regulated the EMT in hepatoma cells remains to be elucidated, and searching drugs to inhibit TGF-beta 1 induced EMT may be considered to be a potentially effective therapeutic strategy in HCC. Fortunately, in this study, we found that curcumin inhibited TGF-beta 1-induced EMT in hepatoma cells. Furthermore, we demonstrated that curcumin inhibited TGF-beta 1-induced EMT via inhibiting Smad2 phosphorylation and nuclear translocation, then suppressing Smad2 combined with the promoter of Snail which inhibited the transcriptional expression of Snail. These findings suggesting curcumin could be a useful agent for antitumor therapy and also a promising drug combined with other strategies to preventing and treating HCC.