title: Sulforaphene inhibits triple negative breast cancer through activating tumor suppressor Egr1.
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.
authors.affiliation: 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.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Wendi
authors.initials: W
authors.lastname: Teng
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.affiliation: 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.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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. yuanqp@mail.buct.edu.cn.
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017879:Isothiocyanates; C473643:sulphoraphene
keywords: Egr1; Isothiocyanate; Sulforaphene; Triple Negative Breast Cancer