2. Academic Validation
  3. A novel sulfonamide derivative suppresses gastrointestinal cancer progression by targeting Axin2 and β-catenin

A novel sulfonamide derivative suppresses gastrointestinal cancer progression by targeting Axin2 and β-catenin

  • Sci Rep. 2025 Nov 25;15(1):41858. doi: 10.1038/s41598-025-25904-6.
Xiaojie Li # 1,  Huijuan Wen # 1,  Le Chang # 1,  Xia Xue 1,  Huayuan Xi 1,  Ruoyu Hu 1,  Mengke Rong 1,  Pengyuan Zheng 2,  Simeng Liu 3
Affiliations

Affiliations

  • 1 Henan Key Laboratory for Helicobacter pylori and Digestive Tract Microecology, The Fifth Affiliated Hospital of Zhengzhou University; Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Science; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, People's Republic of China.
  • 2 Henan Key Laboratory for Helicobacter pylori and Digestive Tract Microecology, The Fifth Affiliated Hospital of Zhengzhou University; Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Science; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, People's Republic of China. [email protected].
  • 3 Henan Key Laboratory for Helicobacter pylori and Digestive Tract Microecology, The Fifth Affiliated Hospital of Zhengzhou University; Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Science; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 41290904 DOI: 10.1038/s41598-025-25904-6
Abstract

Gastrointestinal Cancer is a major global health risk with rising incidence and limited effective therapeutic options. Despite advancements in diagnostics and therapies, the aggressive nature of these malignancies make novel therapeutic strategies essential. This study synthesized and evaluated a novel sulfonamide derivative, compound 2406, for its antiproliferative effects in gastrointestinal Cancer cell lines (EC-9706, SGC-7901, and HT-29). Molecular docking and biological assays were conducted to assess its potential binding and interaction with β-tubulin and the Wnt/β-catenin signaling pathway, with a focus on EC-9706 and HT-29 cell lines. Compound 2406 significantly inhibited tumor cell invasion, migration, and colony formation. It induced G2/M phase cell cycle arrest in EC-9706 and HT-29 cells, reducing cellular proliferation. Molecular docking and in vitro experiments confirmed that compound 2406 interfered with β-tubulin cytoskeletal integrity and suppressed Wnt/β-catenin signaling, which is critical for tumor progression. These findings highlight the therapeutic potential of compound 2406 as a novel Anticancer agent targeting β-tubulin and Wnt/β-catenin signaling in gastrointestinal Cancer. Further in vivo studies would be warranted to validate its efficacy and clinical applicability.

Keywords

Anti-cancer; Derivative 2406; Gastrointestinal cancer; Sulfonamide; Wnt/β-catenin; β-tubulin.

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