MnTE-2-PyP attenuates TGF-β-induced epithelial-mesenchymal transition of colorectal cancer cells by inhibiting the Smad2/3 signaling pathway

Yu Yang, Pei Zhang, Ruicheng Yan, Qi Wang, Erhu Fang, Hongxue Wu, Shijun Li, Haiyan Tan, Xing Zhou, Xianxiong Ma, Yu Tang, Yongming Huang, Rui Deng, Ying Liu, Shilun Tong, Zhihua Wang, Rebecca E Deegan, Qiang Tong

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number8639791
JournalOxidative medicine and cellular longevity
Volume2019
DOIs
StatePublished - Jan 1 2019

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Epithelial-Mesenchymal Transition
Transforming Growth Factors
Colorectal Neoplasms
Cells
Smad2 Protein
Assays
manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin
Gastropoda
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Snails
Manganese
Antineoplastic Agents
Wound Healing
Colonic Neoplasms
Superoxide Dismutase
Cell Movement
Names
Real-Time Polymerase Chain Reaction
Western Blotting

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

Cite this

MnTE-2-PyP attenuates TGF-β-induced epithelial-mesenchymal transition of colorectal cancer cells by inhibiting the Smad2/3 signaling pathway. / Yang, Yu; Zhang, Pei; Yan, Ruicheng; Wang, Qi; Fang, Erhu; Wu, Hongxue; Li, Shijun; Tan, Haiyan; Zhou, Xing; Ma, Xianxiong; Tang, Yu; Huang, Yongming; Deng, Rui; Liu, Ying; Tong, Shilun; Wang, Zhihua; Deegan, Rebecca E; Tong, Qiang.

In: Oxidative medicine and cellular longevity, Vol. 2019, 8639791, 01.01.2019.

Research output: Contribution to journalArticle

Yang, Y, Zhang, P, Yan, R, Wang, Q, Fang, E, Wu, H, Li, S, Tan, H, Zhou, X, Ma, X, Tang, Y, Huang, Y, Deng, R, Liu, Y, Tong, S, Wang, Z, Deegan, RE & Tong, Q 2019, 'MnTE-2-PyP attenuates TGF-β-induced epithelial-mesenchymal transition of colorectal cancer cells by inhibiting the Smad2/3 signaling pathway', Oxidative medicine and cellular longevity, vol. 2019, 8639791. https://doi.org/10.1155/2019/8639791
Yang, Yu ; Zhang, Pei ; Yan, Ruicheng ; Wang, Qi ; Fang, Erhu ; Wu, Hongxue ; Li, Shijun ; Tan, Haiyan ; Zhou, Xing ; Ma, Xianxiong ; Tang, Yu ; Huang, Yongming ; Deng, Rui ; Liu, Ying ; Tong, Shilun ; Wang, Zhihua ; Deegan, Rebecca E ; Tong, Qiang. / MnTE-2-PyP attenuates TGF-β-induced epithelial-mesenchymal transition of colorectal cancer cells by inhibiting the Smad2/3 signaling pathway. In: Oxidative medicine and cellular longevity. 2019 ; Vol. 2019.
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abstract = "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.",
author = "Yu Yang and Pei Zhang and Ruicheng Yan and Qi Wang and Erhu Fang and Hongxue Wu and Shijun Li and Haiyan Tan and Xing Zhou and Xianxiong Ma and Yu Tang and Yongming Huang and Rui Deng and Ying Liu and Shilun Tong and Zhihua Wang and Deegan, {Rebecca E} and Qiang Tong",
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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 - Deegan, Rebecca E

AU - Tong, Qiang

PY - 2019/1/1

Y1 - 2019/1/1

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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