ArticleBiological procedures online2026
Astragaloside IV Suppresses Gastric Cancer by m6A-dependent FSP1 Modulation and Ferroptosis Induction.
Article in Biological procedures online, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Gene Variations in RNA Modification Pathway Linked to Poor Survival After Gastric Cancer Surgery.Genes · 2026Article
- Reader-dependent functional duality of FTO: a context-switching node at the intersection of immune evasion and therapeutic resistance.Frontiers in immunology · 2026Review
- Ferroptosis suppressor protein 1-mediated ferroptosis suppression in sepsis: non-canonical antioxidant pathways, inflammatory regulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Mechanism and therapeutic prospects of ferroptosis regulation through m6A in cancer.Frontiers in cell and developmental biology · 2026Review
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7 authors.
Funding
Abstract
backgroundAstragaloside IV (AS-IV), a key active component derived from the traditional Chinese medicinal plant Astragali, has been reported to exhibit various biological activities, including antioxidative, anti-inflammatory, immunoregulatory, and antineoplastic properties. This study aimed to elucidate the role of AS-IV in inhibiting gastric cancer (GC) growth, focusing on its impact on cell ferroptosis and the underlying molecular mechanisms.
methodsProliferation and migration of GC cells upon AS-IV treatment were examined using CCK-8, colony formation, and Transwell assays. Ferroptosis induction was analyzed via ELISA, flow cytometry, and transmission electron microscopy. Ferroptosis suppressor protein 1 (FSP1) mRNA stability was assessed by the ActD assay, while RNA immunoprecipitation (RIP) was employed to confirm the interaction between FSP1 mRNA, Fat mass and obesity-associated protein (FTO) demethylase, and YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2). The dual-luciferase reporter assay was used to explore FTO binding to N6-methyladenosine (m6A)-modified sites on FSP1 mRNA. Furthermore, AS-IV’s anti-tumor effects (20 mg/kg) were validated in vivo using gastric cancer xenograft and lung metastasis mouse models.
resultsAS-IV significantly suppressed the proliferation and migration of GC cells by inducing ferroptosis. Mechanistically, AS-IV down-regulated FTO, thus impairing its interaction with FSP1 mRNA and leading to increased m6A modification on FSP1 mRNA. This modification facilitated m6A recognition protein YTHDF2-mediated recognition and subsequent degradation of FSP1 mRNA. The reduction of FSP1 triggered ferroptosis, while the overexpression of FSP1 or inhibition of ferroptosis by ferrostatin-1 partially reversed AS-IV’s effects on cell viability and migration. In vivo, AS-IV effectively inhibited tumor growth and metastasis.
conclusionsThis study highlights potent anti-GC effects of AS-IV, mediated by the suppression of FSP1 via the FTO/YTHDF2/m6A axis.
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