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Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-β signaling pathways

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Abstract

Inflammation is one of the characteristic features during the development of human tumors. A pro-inflammatory cytokine that is known to promote inflammation during cancer development is the transforming growth factor-β (TGF-β). On the other hand, demethylzeylasteral (T-96) is a natural compound isolated from Tripterygium wilfordii Hook F, which has been reported to have various pharmacological properties including anti-inflammatory and immunosuppressive activities. We investigated the effects of T-96 on the highly metastatic breast cancer cell line, MDA-MB-231. Cell migration was assessed by scratch-wound migration assay, and the molecular mechanisms underlying the effects of T-96 were examined by qPCR and Western blot analyses. We also investigated the suppression effects of T-96 on the pulmonary metastasis in the 4T1 mouse model. T-96 inhibited TGF-β-induced migration and epithelial–mesenchymal transition both in vitro and in vivo. These results demonstrate that T-96 inhibited invasion of MDA-MB-231 and 4T1 cells via suppressing the canonical and non-canonical TGF-β signaling pathways.

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Author contribution

C Xu, H Cheng, and M Wu conceived and designed the research. L Liu, Y Ji, and J Fan conducted the experiments. L Li and Y Ji analyzed the data. F Li and Y Li contributed to the revision. C Xu wrote the manuscript. All the authors read and approved the manuscript.

Funding

This work was financially supported by the Young Scientists Fund of the National Natural Science Foundation of China (No. 81302829, 81500530, 81500544), Fund of the National Natural Science Foundation of China (No. 81373511, 81573910), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Author notes

  1. Liu Li, Yi Ji, and Junting Fan contributed equally to this work and are to be considered the first authors.

Authors and Affiliations

  1. The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Liu Li, Yi Ji, Mianhua Wu, Haibo Cheng & Changliang Xu

  2. School of Pharmacy, Nanjing Medical University, Nanjing, 210023, China

    Junting Fan

  3. Department of Nephrology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    Furong Li & Yan Li

  4. The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China

    Mianhua Wu, Haibo Cheng & Changliang Xu

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  1. Liu Li
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  2. Yi Ji
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  3. Junting Fan
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  5. Yan Li
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Correspondence to Mianhua Wu, Haibo Cheng or Changliang Xu.

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All animal experiments were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals with the approval of the Nanjing University of Chinese Medicine, Nanjing.

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Li, L., Ji, Y., Fan, J. et al. Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-β signaling pathways. Naunyn-Schmiedeberg's Arch Pharmacol 392, 593–603 (2019). https://doi.org/10.1007/s00210-019-01614-5

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