Abstract
Platelet activation by tumor cells contributes to cancer progression through enhanced invasion, metastasis, and immune evasion. The study assessed the effect of ononin, an isoflavone glycoside of the Fabaceae family, on tumor-induced platelet activation, invasion, cell-cycle progression, and apoptosis in MDA-MB-231 breast cancer cells. Platelet activation was measured using flow cytometry. A 3D spheroid assay was used to evaluate invasion while cell-cycle distribution was analyzed with propidium iodide staining. Apoptosis was detected using Annexin V/propidium iodide labeling. Flow cytometry showed that platelets incubated with MDA-MB-231 cells displayed a marked increase in CD42⁺/CD62P⁺ double-positive events, confirming platelet activation. Pretreatment of MDA-MB-231 cells with ononin (25 or 37 µM) significantly attenuated their ability to activate platelets (p < 0.01), with no difference between the two concentrations. Invasion assays revealed that both concentrations of ononin markedly reduced the invasive capacity of spheroids over five days (p < 0.0001 for both). Cell cycle analysis indicated a dose-dependent G1-phase arrest, accompanied by a reduction in the proportions of cells in S and G2 phases (p < 0.0001 for both). Furthermore, ononin (25 and 37 µM) decreased viable cell percentages (p < 0.0001) while increasing late apoptotic populations (p < 0.05 and p < 0.01, respectively). Early apoptosis increased significantly at 37 µM (p < 0.05), whereas necrosis was higher at 25 µM (p < 0.05) compared to control. These findings indicate that ononin decreases tumor-induced platelet activation, suppresses invasion, induces G1 arrest, and promotes apoptosis in MDA-MB-231 cells, supporting its potential as a therapeutic candidate for aggressive breast cancers.
Data availability
No datasets were generated or analysed during the current study.
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M.A.: supervision and writing original draft, A.K.: supervision and reviewing & editing original draft, N.S., D.Q., D.A., S.A.: Methodology and data curation, S.S.: reviewing the original draft, N.S.: Statistical analysis, W.S.: supervision and resources.
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Al-Kabariti, A.Y., Abbas, M.A., Alsarayreh, N. et al. Ononin suppresses tumor-induced platelet activation and invasion and enhances cell-cycle arrest and apoptosis in triple-negative breast cancer cells. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36762-1
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DOI: https://doi.org/10.1038/s41598-026-36762-1
