Diallyl disulfide inhibits proliferation, epithelial—mesenchymal transition, and invasion through RORα-mediated downregulation of Wnt1/β-catenin pathway in gastric cancer cells

Authors

Jian Su, Department of Pathology, Second Affiliated Hospital, University of South China, China
Hui He, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China
Yu-Kun Li, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China
Hong Xia, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China
Fang Liu, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China
Ying Zeng, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China
Xi Zeng, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China
Hui Ling, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China
Bo Su, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, ChinaFollow
Qi Su, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, China

Keywords

Diallyl disulfide; Gastric cancer cell epithelial-mesenchymal transition; Proliferation; RORα; Wnt/β-catenin pathway

Abstract

Overactivation of Wnt/β-catenin pathway due to dysfunction of retinoid-related orphan receptor α (RORα) is related to cancer development and progression. Diallyl disulfide (DADS), an active component of garlic, has been reported in our previous study for upregulation of RORα expression in gastric cancer (GC) cells. It remains to be elucidated the role and mechanism of RORα in DADS against GC. This study revealed that DADS treatment resulted in reduced expression levels of Wnt1, β-catenin, TCF-4, intranuclear β-catenin and p-β-catenin in GC cells, concomitant with the compromised expression of β-catenin target genes (Axin, c-Jun, and c-Myc). RORα overexpression augmented DADS-induced downregulation of Wnt1/β-catenin pathway, G2/M phase arrest, and cell growth inhibition in vitro and in vivo. Contrarily, knockdown of RORα attenuated these effects of DADS. Interestingly, DADS induced an increase in the binding of RORα to β-catenin, which may lead to reduction of β-catenin phosphorylation and nuclear translocation. This interplay modulated by DADS may affect β-catenin target gene expression for that the opposite results were observed in DADS-treated RORα knockdown and overexpression cells. DADS caused a decrease in vimentin, snail and MMP-9, as well as an increase in E-cadherin and TIMP3 expression, which restricted epithelial‑mesenchymal transition (EMT), migration, and invasion. The aforementioned effects of DADS were weakened simultaneously when the suppression of DADS on the Wnt1/β-catenin pathway was resisted by knockdown of RORα. In contrast, overexpression of RORα enhanced the effects of DADS. Therefore, RORα-mediated downregulation of Wnt1/β-catenin pathway could undertake an important role in anticancer activity of DADS against GC cell proliferation, EMT, migration, and invasion.

Abstract Image

Recommended Citation

Su, Jian; He, Hui; Li, Yu-Kun; Xia, Hong; Liu, Fang; Zeng, Ying; Zeng, Xi; Ling, Hui; Su, Bo; and Su, Qi (2022) "Diallyl disulfide inhibits proliferation, epithelial—mesenchymal transition, and invasion through RORα-mediated downregulation of Wnt1/β-catenin pathway in gastric cancer cells," Journal of Food and Drug Analysis: Vol. 30 : Iss. 3 , Article 12.
Available at: https://doi.org/10.38212/2224-6614.3424

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