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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cadherins / metabolism*
  • Cadherins / physiology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disease Progression
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / metabolism
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Isothiocyanates / metabolism
  • Isothiocyanates / pharmacology*
  • MAP Kinase Kinase 3 / genetics
  • MAP Kinase Kinase 3 / metabolism
  • MAP Kinase Signaling System / genetics
  • Mice
  • Mice, Nude
  • Stearoyl-CoA Desaturase / metabolism*
  • Stearoyl-CoA Desaturase / physiology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antigens, Differentiation
  • Antineoplastic Agents
  • Cadherins
  • GADD45B protein, human
  • Isothiocyanates
  • Tumor Suppressor Protein p53
  • Stearoyl-CoA Desaturase
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 3
  • MAP2K3 protein, human
  • sulphoraphene