ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1546157
This article is part of the Research TopicMolecular Mechanisms of Platelet Aggregation and Modulation with Herbal Medicine TreatmentView all 3 articles
1,8-cineole inhibits platelet-leukocyte aggregate formation by reducing P-selectin expression
Provisionally accepted
- Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Technical University of Munich, Munich, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Platelets, traditionally recognized for their role in hemostasis, have increasingly been implicated in cancer progression, including head and neck squamous cell carcinoma (HNSCC). Beyond releasing growth factors and chemokines, platelets modulate leukocyte-mediated proinflammatory responses and effector functions through direct or indirect contact. These processes promote tumor cell proliferation, survival, epithelial to mesenchymal transition (EMT) and extravasation. Consequently, targeting platelet-leukocyte aggregate (PLA) formation represents a promising pharmacological strategy to interfere with platelet-mediated pro-tumorigenic effects. 1,8-cineole, a plant-derived metabolite found in several botanical sources, has shown potent anti-platelet effects through modulation of the adenosine A2A receptor signaling. However, its influence on PLA formation has not been investigated. In this study, we analyzed platelet activation and PLA formation in HNSCC patients compared to healthy donors. A co-culture system combined with blocking antibodies was employed to elucidate the mechanisms of PLA formation. Moreover, the pharmacological effects of 1,8-cineole were compared with those of conventional anti-platelet drugs. The results revealed elevated P-selectin expression and enhanced PLA formation in HNSCC patients. PLA formation was predominantly mediated through P-selectin-PSGL-1 interactions. Ex vivo studies demonstrated that 1,8-cineole significantly reduced PLA formation by inhibiting P-selectin expression on platelets. Notably, traditional anti-platelet agents did not significantly inhibit PLA formation, despite effectively reducing platelet aggregation. These findings identify a pharmacological effect of 1,8-cineole in disrupting platelet-leukocyte interactions via suppression of the P-selectin-PSGL-1 axis. This suggests that 1,8-cineole offers potential pharmacological benefits in mitigating platelet-mediated inflammation and tumor progression.
Keywords: platelets, Platelet-leukocyte aggregates, Anti-platelet drugs, Head and neck squamous cell carcinoma, PubChem CID=2758)
Received: 16 Dec 2024; Accepted: 25 Apr 2025.
Copyright: © 2025 Petry, Mai, Shoykhet, Bashiri Dezfouli and Wollenberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Barbara Wollenberg, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Technical University of Munich, Munich, Germany
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.