ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1598520
This article is part of the Research TopicFerroptosis, Cuproptosis, and Triaptosis: Unveiling Pathways and Translational ProspectsView all 9 articles
Perillaldehyde synergizes with ferroptosis inducers to promote ferroptotic cell death in gastric cancer
Provisionally accepted
Rui Wang
Jin-Fen CuiJing LvJia-Lin SongYang-Yang LuXiao-Juan HuangZhong-Kun LinSi-Yi Zhang
Sha-Sha Wang*
Wensheng Qiu*- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 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
As a traditional medicine and food homologous plant, Perilla frutescens is widely cultivated in China, Japan, and Korea. According to the Compendium of Materia Medica, the leaves, stems, and seeds of perilla can all be used as medicine. Perilla essential oil has been used in traditional Chinese medicine since ancient times. It has been demonstrated that perillaldehyde (PAH), a primary composition of the essential oil extracted from perilla, can inhibit tumor growth through multiple mechanisms. However, the specific mechanisms by which PAH suppresses gastric cancer remain incompletely understood. In this study, PAH was proven to inhibit the growth of gastric cancer both in vivo and in vitro. It led to a reduction in mitochondrial membrane potential (MMP), an augmentation of the accumulation of reactive oxygen species (ROS), and an elevation of oxidative stress levels. Moreover, PAH decreased intracellular glutathione (GSH) levels while increasing intracellular lipid peroxidation and Fe2+ levels. These effects indicate that PAH induces ferroptosis via inhibiting the system Xc (-)/GSH/GPX4 axis. Furthermore, PAH influenced the expression of proteins related to iron transport and storage and regulated ferroptosis via the P62-Keap1-Nrf2 pathway. When combined with the ferroptosis agonist RSL3, PAH could promote ferroptosis in gastric cancer. This suggests a potential therapeutic strategy in which PAH could be used to synergize with ferroptosis inducers for treating gastric cancer.
Keywords: Natural Products, Perillaldehyde, gastric cancer, Oxidative Stress, ferroptosis
Received: 23 Mar 2025; Accepted: 22 May 2025.
Copyright: © 2025 Wang, Cui, Lv, Song, Lu, Huang, Lin, Zhang, Wang and Qiu. 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:
Sha-Sha Wang, Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
Wensheng Qiu, Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
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.