ArticleInternational journal of molecular sciences2026
Targeting Lung Cancer Stem Cells with Trimebutine: Synergistic Antitumor Activity in Combination with Cisplatin.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Lung cancer recurrence and therapeutic resistance are driven by cancer stem cells (CSCs), yet clinically available CSC-targeted therapies remain lacking. To identify actionable anti-CSC agents, we screened 1018 FDA-approved drugs using a 3D sphere culture system enriching lung CSC-like cells. Trimebutine, a gastrointestinal motility regulator targeting G-protein-coupled receptors (GPCRs), was identified as a potent agent with over 49.5-fold higher selectivity toward lung CSC-like cells (SI > 49.55) compared with standard therapies such as cisplatin (SI = 1.39) and gefitinib (SI = 1.00). In H460-SP spheres, trimebutine markedly impaired sphere-forming capacity, reduced cell viability, and downregulated key CSC surface markers (CD133, CD44) alongside stemness regulators (c-MYC, EpCAM, BMI1, OCT3/4, NANOG, SOX2, SMAD3). Mechanistically, trimebutine suppressed overexpressed calcium and potassium channels (
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