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Diallyl trisulphide, a H 2 S donor, compromises the stem cell phenotype and restores thyroid‐specific gene expression in anaplastic thyroid carcinoma cells by targeting AKT‐SOX2 axis
Author(s) -
Zhang Li,
Xu Shichen,
Cheng Xian,
Zheng Jiangxia,
Wang Yunping,
Wu Jing,
Wang Xiaowen,
Wu Liying,
Yu Huixin,
Bao Jiandong
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.7065
Subject(s) - cancer research , sox2 , protein kinase b , gene knockdown , thyroid cancer , stem cell , cell growth , anaplastic thyroid cancer , cancer stem cell , cancer cell , biology , chemistry , thyroid , cancer , medicine , cell culture , endocrinology , signal transduction , microbiology and biotechnology , gene , biochemistry , genetics , transcription factor
It is widely accepted that anaplastic thyroid carcinoma (ATC), a rare, extremely aggressive malignant, is enriched by cancer stem cells (CSCs), which are closely related to the pathogenesis of ATC. In the present study, we demonstrated that diallyl trisulphide (DATS), a well‐known hydrogen sulphide (H 2 S) donor, suppressed sphere formation and restored the expression of iodide‐metabolizing genes in human ATC cells, which were associated with H 2 S generation. Two other H 2 S donors, NaHS and GYY4137, could also suppress the self‐renewal properties of ATC cells in vitro. Compared with normal thyroid tissues and papillary thyroid carcinomas (PTCs), the elevated expressions of SOX2 and MYC, two cancer stem cell markers, in ATCs were validated in the combined Gene Expression Omnibus (GEO) cohort. DATS decreased the expression of SOX2, which was mediated by H 2 S generation. Furthermore, knockdown of AKT or inhibition of AKT by DATS led to a decrease of SOX2 expression in ATC cells. AKT knockdown phenocopied restoration of thyroid‐specific gene expression in ATC cells. Our data suggest that H 2 S donors treatment can compromise the stem cell phenotype and restore thyroid‐specific gene expression of ATC cells by targeting AKT‐SOX2 pathway, which may serve as a therapeutic strategy to intervene the CSC progression of ATC.