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Sulforaphene inhibits triple negative breast cancer through activating tumor suppressor Egr1

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Abstract

Sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) is a member of isothiocyanates, which is derived from radish seeds. It has shown that multiple isothiocyanates, such as sulforaphane, can effectively inhibit cancer cell proliferation in vitro and in vivo. However, it is still largely unknown if SFE could impact breast cancer. In this study, we investigated the anticancer effects of SFE on triple negative breast cancer (TNBC) via a series of in vitro and in vivo assays. We found that SFE can significantly inhibit cell proliferation in multiple TNBC cell lines through inducing G2/M phase arrest as well as cell apoptosis. Nude mice xenograft assays support the anti-TNBC role of SFE in vivo. Interestingly, SFE can repress expression of cyclinB1, Cdc2, and phosphorylated Cdc2, and, then, induced G2/M phase arrest of TNBC cells. To identify SFE target genes, we detected genome-wide gene expression changes through gene expression profiling and observed 27 upregulated and 18 downregulated genes in MDA-MB-453 cells treated with SFE. Among these genes, Egr1 was successfully validated as a consistently activated gene after SFE treatment in TNBC MDA-MB-453 and MDA-MB-436 cells. Egr1 overexpression inhibited proliferation of TNBC cells. However, Egr1 knockdown using siRNAs significantly promoted TNBC cell growth, indicating the tumor suppressor nature of Egr1. In sum, we for the first time found that SFE might be a potential anti-TNBC natural compound and its antiproliferation effects might be mediated by tumor suppressor Egr1.

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Grant support

This work was supported by the National High-Tech Research and Development Program of China (2015AA020950); the Fundamental Research Funds for the Central Universities (YS1407); the open project of State Key Laboratory of Molecular Oncology (SKL-KF-2015-05); Program for Changjiang Scholars and Innovative Research Team in University (IRT13045); Innovation and Promotion Project of Beijing University of Chemical Technology.

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    Authors and Affiliations

    1. State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, P. O. Box 75, 100029, Beijing, China

      Ming Yang, Wendi Teng, Yue Qu, Haiyong Wang & Qipeng Yuan

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    1. Ming Yang
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    2. Wendi Teng
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    3. Yue Qu
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    4. Haiyong Wang
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    5. Qipeng Yuan
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    Correspondence to Qipeng Yuan.

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    The authors declare no competing financial interests.

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    Ming Yang, Wendi Teng and Yue Qu have contributed equally to this work.

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    Yang, M., Teng, W., Qu, Y. et al. Sulforaphene inhibits triple negative breast cancer through activating tumor suppressor Egr1 . Breast Cancer Res Treat 158, 277–286 (2016). https://doi.org/10.1007/s10549-016-3888-7

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    • DOI: https://doi.org/10.1007/s10549-016-3888-7

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