Ononin suppresses tumor-induced platelet activation and invasion and enhances cell-cycle arrest and apoptosis in triple-negative breast cancer cells

Q: What is the main focus of the study?

The study examines how ononin affects tumor-induced platelet activation, invasion, cell-cycle progression, and apoptosis in MDA-MB-231 triple-negative breast cancer cells.

Q: How was platelet activation measured?

Platelet activation was measured using flow cytometry, including CD42+/CD62P double-positive events.

Q: What cell-cycle effect did ononin produce?

Ononin induced a dose-dependent G1-phase arrest and reduced the proportions of cells in S and G2 phases.

Sep 22, 2026

Upload by Theodore

Platelet activation driven by tumor cells promotes cancer progression by increasing invasion, metastasis, and immune evasion. This study evaluates ononin, an isoflavone glycoside from the Fabaceae family, and its effects on tumor-induced platelet activation, invasion, cell-cycle progression, and apoptosis in MDA-MB-231 triple-negative breast cancer cells. Flow cytometry assessed platelet activation, 3D spheroid assays measured invasion, and cell-cycle distribution and apoptosis were analyzed using propidium iodide staining and Annexin V/propidium iodide labeling. Ononin pretreatment (25–37 µM) reduced platelet activation signals, suppressed invasion over five days, induced dose-dependent G1 arrest, lowered viable cells, and increased late apoptotic populations, supporting its therapeutic potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Background and Rationale

Platelet–tumor interactions in metastasis

Experimental Approach

Effects of ononin on platelet activation

Invasion assessment using 3D spheroids

Cell-cycle and apoptosis analyses

Results

Platelet activation modulation

Invasion suppression

G1-phase arrest and apoptosis induction

Conclusion and Therapeutic Implications

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Ononin suppresses tumor-induced platelet activation and invasion and enhances cell-cycle arrest and apoptosis in triple-negative breast cancer cells AyaY. Al-Kabariti1,2􀀍, ManalA. Abbas2,3􀀍, NowarAlsarayreh4, Dana A. Alqudah4, Duaa Abuarqoub5,6, Saba Hussein Atieh2, Sneha Smarakan7 & Walhan al Shaer4 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 tumorinduced platelet activation, suppresses invasion, inducesG1 arrest, and promotes apoptosis in MDAMB-231 cells, supporting its potential as a therapeutic candidate for aggressive breast cancers. Keywords Apoptosis, Cell cycle, Invasion, Ononin, Platelets, Tumor-induced platelet aggregation Metastasis remains the primary cause of death in cancer patients and results from intricate communication between tumor cells and their surrounding microenvironment1. Among the critical players in this process are platelets. It has been shown that platelets support tumor cell migration, invasion, survival in circulation, and eventual colonization of distant organs. When activated by tumor cells, platelets can drive epithelial– mesenchymal transition (EMT) through the release of pro-metastatic factors such as TGF-β1. They also form protective clusters with circulating tumor cells, shielding them from immune attack and facilitating vascular extravasation2,3. Moreover, tumor-derived nucleic acids recruit and activate platelets at dysregulated vasculature, fostering immune suppression. Notably, disrupting platelet–leukocyte interactions inhibited tumor progression with efficacy comparable to systemic checkpoint blockade4. 1Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan. 2Pharmacological and Diagnostic Research Centre, Al-Ahliyya Amman University, Amman 19328, Jordan. 3Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan. 4Cell Therapy Center, The University of Jordan, Amman, Jordan. 5Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan. 6Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, USA. 7School of Pharmacy and Medical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK. 􀀍 [email: A.kabariti@ammanu.edu.jo](email: A.kabariti@ammanu.edu.jo); [m.abbas@ammanu.edu.jo](m.abbas@ammanu.e

FAQs

What is the main focus of the study?

The study examines how ononin affects tumor-induced platelet activation, invasion, cell-cycle progression, and apoptosis in MDA-MB-231 triple-negative breast cancer cells.

How was platelet activation measured?

Platelet activation was measured using flow cytometry, including CD42+/CD62P double-positive events.

What cell-cycle effect did ononin produce?

Ononin induced a dose-dependent G1-phase arrest and reduced the proportions of cells in S and G2 phases.

Sep 22, 2026

Upload by Theodore