MnTE-2-PyP Attenuates TGF-β-Induced Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Inhibiting the Smad2/3 Signaling Pathway

Background. As a key step in enhancing cancer cell invasion and metastasis, epithelial-mesenchymal transition (EMT) plays an important role in colorectal cancer progression. EMT is triggered by a variety of signaling pathways, among which the transforming growth factor beta (TGF-beta) signaling pathway has been implicated as a primary inducer. Accumulating evidence demonstrates that MnTE-2-PyP (chemical name: manganese(III) meso-tetralcis-(N-ethylpyridinium-2-yl), a superoxide dismutase (SOD) mimetic, inhibits TGF-beta signaling; however, its ability to inhibit TGF-beta-induced EMT in colorectal cancer has not yet been explored. Methods. To verify our hypothesis that MnTE-2-PyP attenuates TGF-beta-induced EMT, human colorectal cancer cells were treated with TGF-beta in the presence or absence of MnTE-2-PyP. Cells were analyzed by several techniques including western blotting, real-time quantitative PCR, transwell assay, and wound healing assay. Results. MnTE-2-PyP reverses cell phenotypes induced by TGF-beta in colon cancer cells. MnTE-2-PyP treatment significantly reduced the expression of mesenchymal markers but maintained epithelial marker expression. Mechanistically, MnTE-2-PyP suppressed the phosphorylated Smad2/3 protein levels induced by TGF-beta in SW480 cells, but MnTE-2-PyP failed to suppress TGF-beta-induced Slug and Snail expression in colorectal cells. Furthermore, MnTE-2-PyP effectively suppressed TGF-beta-mediated cell migration and invasion and the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in colorectal cells. Conclusion. Taken together, we provide an in-depth mechanism by which MnTE-2-PyP inhibits colorectal cancer progression, supporting an important role for MnTE-2-PyP as an effective and innovative antitumor agent to enhance treatment outcomes in colorectal cancer.