2. Academic Validation
  3. Sulforaphene inhibits esophageal cancer progression via suppressing SCD and CDH3 expression, and activating the GADD45B-MAP2K3-p38-p53 feedback loop

Sulforaphene inhibits esophageal cancer progression via suppressing SCD and CDH3 expression, and activating the GADD45B-MAP2K3-p38-p53 feedback loop

  • Cell Death Dis. 2020 Sep 1;11(8):713. doi: 10.1038/s41419-020-02859-2.
Sichong Han 1,  Yandong Wang 1,  Jie Ma 2,  Zhe Wang 1,  Hui-Min David Wang 3 4 5 6 7,  Qipeng Yuan 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, P.R. China.
  • 2 Department of Biotherapy, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, P.R. China.
  • 3 Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung City, 402, Taiwan. davidw@dragon.nchu.edu.tw.
  • 4 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City, 404, Taiwan. davidw@dragon.nchu.edu.tw.
  • 5 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, 807, Taiwan. davidw@dragon.nchu.edu.tw.
  • 6 College of Food and Biological Engineering, Jimei University, Xiamen City, 361021, Fujian Province, P.R. China. davidw@dragon.nchu.edu.tw.
  • 7 Undergraduate Program Study of Biomedical Engineering, Physics Department, Airlangga University, Surabaya City, 60115, Indonesia. davidw@dragon.nchu.edu.tw.
  • 8 State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, P.R. China. yuanqp@mail.buct.edu.cn.
PMID: 32873775 DOI: 10.1038/s41419-020-02859-2
Abstract

Esophageal Cancer is one of the most common Cancer with limited therapeutic strategies, thus it is important to develop more effective strategies to against it. Sulforaphene (SFE), an isothiocyanate isolated from radish seeds, was proved to inhibit esophageal Cancer progression in the current study. Flow cytometric analysis showed SFE induced cell Apoptosis and cycle arrest in G2/M phase. Also, scrape motility and transwell assays presented SFE reduced esophageal Cancer cell metastasis. Microarray results showed the influence of SFE on esophageal Cancer cells was related with stearoyl-CoA desaturase (SCD), cadherin 3 (CDH3), mitogen-activated protein kinase kinase 3 (MAP2K3) and growth arrest and DNA damage inducible beta (GADD45B). SCD and CDH3 could promote esophageal Cancer metastasis via activating the Wnt pathway, while the latter one was involved in a positive feedback loop, GADD45B-MAP2K3-p38-p53, to suppress esophageal Cancer growth. GADD45B was known to be the target gene of p53, and we proved in this study, it could increase the phosphorylation level of MAP2K3 in esophageal Cancer cells, activating p38 and p53 in turn. SFE treatment elevated MAP2K3 and GADD45B expression and further stimulated this feedback loop to better exert antitumor effect. In summary, these results demonstrated that SFE had the potential for developing as a chemotherapeutic agent because of its inhibitory effects on esophageal Cancer metastasis and proliferation.

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