ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicEpigenetic Regulation in Cancer: Mechanisms, Implications, and Therapeutic InterventionsView all 11 articles
Paeonol inhibits the development of oral squamous cell carcinoma through the PI3K/AKT signaling pathway
Provisionally accepted
Changyue Liu1,2
Xuelin Mou1,2Jiaming Liu1,2
Wu Yuehan2,3Jinpeng Han1,4Ren Li1,2Yuxia Gao1,2
Ying Liu1,2*- 1Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- 2North Sichuan Medical College, Nanchong, China
- 3The First Affiliated Hospital of Nanchang University, Nanchang, China
- 4Changsha Medical University, Changsha, China
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
Background: Paeonol (Pae), a phenolic bioactive compound extracted from Cortex Moutan, exhibits numerous pharmacological properties, including anti-inflammatory, immunomodulatory, and antitumor activities. However, the precise mechanisms by which Pae influences protective autophagy in oral squamous cell carcinoma (OSCC) remain incompletely characterized. Methods: This study assessed the effects of Pae treatment on proliferation, migration, and invasive potential of OSCC cells in vitro. Network pharmacology was employed to identify potential molecular targets of Pae involved in OSCC. Autophagic flux was analyzed using transmission electron microscopy alongside a dual-fluorescence reporter assay. Additionally, the combined effects of Pae with autophagy inhibitors were investigated. Results: Pae treatment promoted mitochondrial-dependent apoptosis and effectively inhibited epithelial–mesenchymal transition (EMT) by attenuating phosphorylation within the PI3K/AKT signaling pathway. Pae simultaneously initiated protective autophagy, confirmed by intact autophagic flux observed in CAL-27 and HSC-3 cells. Interference with this autophagic process through the autophagy inhibitor 3-methyladenine (3-MA) intensified apoptotic activity and markedly reduced OSCC cell proliferation. Conclusion: Pae suppressed OSCC cell proliferation and EMT and was associated with mitochondrial apoptosis and activation of autophagic flux, accompanied by reduced PI3K/AKT phosphorylation. Co-treatment with 3-methyladenine (3-MA) further decreased cell viability and enhanced apoptosis-associated changes, suggesting that pharmacological co-targeting of PI3K signaling and autophagy may potentiate Pae’s antitumor activity. Further studies are warranted to delineate the relative contributions of apoptosis and autophagy to Pae-induced cytotoxicity in OSCC.
Keywords: Autophagy, Drug Development, Networkpharmacology, oral squamous cell carcinoma, paeonol
Received: 16 Nov 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Liu, Mou, Liu, Yuehan, Han, Li, Gao and Liu. 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: Ying Liu
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.