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

Autor: Yandong Wang, Zhe Wang, Hui-Min David Wang, Jie Ma, Sichong Han, Qipeng Yuan
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
Esophageal Neoplasms
MAP Kinase Kinase 3
Cell
Gene Expression
Apoptosis
p38 Mitogen-Activated Protein Kinases
Metastasis
Mice
0302 clinical medicine
Cell Movement
Isothiocyanates
Tumour-suppressor proteins
Kinase
Chemistry
lcsh:Cytology
Oesophageal cancer
Wnt signaling pathway
Esophageal cancer
Cadherins
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
030220 oncology & carcinogenesis
Disease Progression
Female
GADD45B
Stearoyl-CoA Desaturase
MAP Kinase Signaling System
Immunology
Mice
Nude
Antineoplastic Agents
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Cell Line
Tumor
medicine
Animals
Humans
lcsh:QH573-671
Cell Proliferation
Cancer
Cell Biology
Oncogenes
medicine.disease
Antigens
Differentiation
Xenograft Model Antitumor Assays
030104 developmental biology
Cancer research
Tumor Suppressor Protein p53
Zdroj: Cell Death and Disease, Vol 11, Iss 8, Pp 1-13 (2020)
Cell Death & Disease
ISSN: 2041-4889
DOI: 10.1038/s41419-020-02859-2
Popis: 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.
Databáze: OpenAIRE
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