TY - JOUR
T1 - MnTE-2-PyP attenuates TGF-β-induced epithelial-mesenchymal transition of colorectal cancer cells by inhibiting the Smad2/3 signaling pathway
AU - Yang, Yu
AU - Zhang, Pei
AU - Yan, Ruicheng
AU - Wang, Qi
AU - Fang, Erhu
AU - Wu, Hongxue
AU - Li, Shijun
AU - Tan, Haiyan
AU - Zhou, Xing
AU - Ma, Xianxiong
AU - Tang, Yu
AU - Huang, Yongming
AU - Deng, Rui
AU - Liu, Ying
AU - Tong, Shilun
AU - Wang, Zhihua
AU - Oberley-Deegan, Rebecca E.
AU - Tong, Qiang
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China Grant No. 81172186 (QT), Natural Science Foundation of Hubei Province Grant No. 2018CFB504 (QT), Guidance Foundation of Renmin Hospital of Wuhan University Grant No. RMYD2018M67 (QT), National Institutes of Health Grant 1R01CA178888 (ROD), the Fred and Pamela Buffett Cancer Center Support Grant P30CA036727 (ROD), Natural Science Foundation of Hubei Province Grant No. 2017CFB179 (PZ), National Science Fund for Excellent Young Scholars Grant No. 81722007 (ZHW), National Science and Technology Major Project No. 2017ZX10304402001008 (ZHW), and Independent Research Project of Wuhan University Grant No. 2042017kf0196 (ZHW).
Publisher Copyright:
© 2019 Yu Yang et al.
PY - 2019
Y1 - 2019
N2 - 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 β (TGF-β) signaling pathway has been implicated as a primary inducer. Accumulating evidence demonstrates that MnTE-2-PyP (chemical name: Manganese(III) meso-tetrakis-(N-ethylpyridinium-2-yl), a superoxide dismutase (SOD) mimetic, inhibits TGF-β signaling; however, its ability to inhibit TGF-β-induced EMT in colorectal cancer has not yet been explored. Methods. To verify our hypothesis that MnTE-2-PyP attenuates TGF-β-induced EMT, human colorectal cancer cells were treated with TGF-β 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-β 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-β in SW480 cells, but MnTE-2-PyP failed to suppress TGF-β-induced Slug and Snail expression in colorectal cells. Furthermore, MnTE-2-PyP effectively suppressed TGF-β-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.
AB - 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 β (TGF-β) signaling pathway has been implicated as a primary inducer. Accumulating evidence demonstrates that MnTE-2-PyP (chemical name: Manganese(III) meso-tetrakis-(N-ethylpyridinium-2-yl), a superoxide dismutase (SOD) mimetic, inhibits TGF-β signaling; however, its ability to inhibit TGF-β-induced EMT in colorectal cancer has not yet been explored. Methods. To verify our hypothesis that MnTE-2-PyP attenuates TGF-β-induced EMT, human colorectal cancer cells were treated with TGF-β 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-β 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-β in SW480 cells, but MnTE-2-PyP failed to suppress TGF-β-induced Slug and Snail expression in colorectal cells. Furthermore, MnTE-2-PyP effectively suppressed TGF-β-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.
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U2 - 10.1155/2019/8639791
DO - 10.1155/2019/8639791
M3 - Article
C2 - 30931081
AN - SCOPUS:85062861263
SN - 1942-0900
VL - 2019
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 8639791
ER -