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A Novel N-Sulfonylamidine-Based Derivative Inhibits Proliferation, Migration, and Invasion in Human Colorectal Cancer Cells by Suppressing Wnt/β-Catenin Signaling Pathway.

ABSTRACT: Wnt signaling has been implicated in the development and metastasis of colorectal cancer (CRC), as well as poorer outcomes. Thus, targeting the Wnt/β-catenin signaling pathway is expected to be a promising treatment option for the therapy of advanced metastatic CRC. A new N-sulfonylamidine derivative (26ag) has been confirmed to suppress the growth of tumor cells by inhibiting C-met, showing strong anti-cancer activity. In this paper, we test the effectiveness of 26ag in suppressing CRC cell proliferation, invasion, and migration. In this regard, 26ag decreased the mRNA and protein expressions of important hallmarks associated with epithelial to mesenchymal transition (EMT). Furthermore, we provide evidence that β-catenin-dependent signaling is involved in 26ag-induced Wnt/β-catenin pathway effects in CRC, using in vitro cell culture and computer docking models. Our study indicates that inhibition of Wnt/β-catenin by a novel compound, 26ag, demonstrates possibility for drug development in the therapy of CRC.

SUBMITTER: Zhao X

PROVIDER: S-EPMC8147639 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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A Novel N-Sulfonylamidine-Based Derivative Inhibits Proliferation, Migration, and Invasion in Human Colorectal Cancer Cells by Suppressing Wnt/β-Catenin Signaling Pathway.

Zhao Xingming X Han Zhuo Z Ma Jiahui J Jiang Shiqing S Li Xia X

Pharmaceutics 20210503 5

Wnt signaling has been implicated in the development and metastasis of colorectal cancer (CRC), as well as poorer outcomes. Thus, targeting the Wnt/β-catenin signaling pathway is expected to be a promising treatment option for the therapy of advanced metastatic CRC. A new N-sulfonylamidine derivative (26ag) has been confirmed to suppress the growth of tumor cells by inhibiting C-met, showing strong anti-cancer activity. In this paper, we test the effectiveness of 26ag in suppressing CRC cell pro ...[more]

PMID: 34063618

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Project description:A previous bioinformatics study suggested that circular RNA 0001666 (circ_0001666) and its target microRNA (miR)-1229 were associated with colorectal cancer (CRC) pathogenesis. However, the role of this interaction in the regulation of CRC cell malignancy remains unclear. Thus, the aim of the present study was to examine the interaction between circ_0001666 and miR-1229, and its effects on CRC cell malignancy. circ_0001666 overexpression or knockdown plasmids were transfected into the HT-29 and HCT-116 cell lines. In addition, in rescue experiments, circ_000166 or miR-1229 overexpression plasmids were transfected into the HT-29 cell line, either alone or in combination. Following transfection, cell proliferation, apoptosis, invasion and the number of CD133+ cells were analyzed. The protein expression level of proteins in the Wnt/β-catenin pathway was also examined. In both HT-29 and HCT-116 cell lines, circ_0001666 overexpression increased apoptosis, whilst inhibiting cell proliferation and invasion, and reducing the frequency of CD133+ cells. By contrast, circ_0001666 knockdown reduced apoptosis, but increased cell proliferation and the number of CD133+ cells. However, cell invasion remained unaffected. In addition, circ_0001666 expression levels negatively regulated those of miR-1229, whereas miR-1229 expression did not affect circ_0001666, in both the HT-29 and HCT-116 cell lines. Furthermore, a luciferase reporter assay confirmed that miR-1229 directly bound to circ_0001666. In the HT-29 cell line, miR-1229 overexpression activated the Wnt/β-catenin pathway, and promoted cell proliferation, invasion and stemness, while suppressing cell apoptosis. In addition, miR-1229 overexpression reversed the effects of circ_0001666 overexpression. In conclusion, circ_0001666 suppresses CRC cell proliferation, invasion and stemness by inhibiting the Wnt/β-catenin signaling pathway by targeting miR-1229, and may represent a potential target for CRC treatment.

Dataset Information

A Novel N-Sulfonylamidine-Based Derivative Inhibits Proliferation, Migration, and Invasion in Human Colorectal Cancer Cells by Suppressing Wnt/β-Catenin Signaling Pathway.

Publications

A Novel N-Sulfonylamidine-Based Derivative Inhibits Proliferation, Migration, and Invasion in Human Colorectal Cancer Cells by Suppressing Wnt/β-Catenin Signaling Pathway.

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