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Ardisiaoside A, a new triterpenoid glycoside from Ardisia gigantifolia, induces cell senescence and targets cancer stem cells in gastric cancer

Year: 2025

Type: article

Abstract: This study aimed to isolate bioactive constituents from Ardisia gigantifolia and assess their effects on gastric cancer stem cells (CSCs) properties. Cytotoxicity and proliferation were quantified using the MTT assay; cell-cycle distribution, CD44 expression, and apoptosis/senescence markers were evaluated by flow cytometry and β-galactosidase staining; reactive oxygen species (ROS) generation and tumorsphere formation were analyzed by fluorescence microscopy and 3D culture; gene expression was measured by qPCR; molecular docking probed interactions with CSCs markers and Notch signaling proteins. Four compounds were isolated, including Ardisiaoside A, β-sitosterol, and two long-chain n-alcohols (octacosan-1-ol, nonacosan-1-ol). Ardisiaoside A was reported from this species for the first time and showed the greatest potency, reducing viability at low micromolar doses (IC 50 : 1.08 ± 0.37 µM in AGS, 2.50 ± 0.72 µM in MKN45 cells). It suppressed migration, induced G2/M arrest, and triggered senescence. CD44 surface levels was markedly reduced, and tumorsphere number and size were inhibited at 2.5 µM. qPCR and immunofluorescence demonstrated notable downregulation of stemness-related genes (OCT4, NANOG) and Notch pathway components, consistent with reduced self-renewal. Molecular docking supported the binding of Ardisiaoside A to NANOG, OCT4, CD44, and Notch proteins (NOTCH1, HES1, DLL1, DLL4), consistent with target inhibition. In conclusion, Ardisiaoside A, a newly identified triterpenoid glycoside from Ardisia gigantifolia , represents a promising candidate that inhibits cell proliferation by reducing cancer stem-cell populations and inducing cellular senescence in gastric cancer. • Ardisiaoside A is a novel triterpenoid glycoside from A. gigantifolia , isolated alongside β-sitosterol and two long-chain n-alcohols. • Ardisiaoside A is potent against gastric cancer cells (IC 50 : 1.08 ± 0.37 µM in AGS, 2.50 ± 0.72 µM in MKN45 cells). • Ardisiaoside A suppresses migration, enforces G2/M arrest, and induces senescence. • Ardisiaoside A attenuates CSC traits by lowering CD44, inhibiting tumorspheres at 2.5 µM, and downregulating OCT4, NANOG, and Notch signaling.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118839