ORIGINAL RESEARCH article
Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1648781
This article is part of the Research TopicEnhancing Cancer Therapy: Integrating Plant-Derived Bioactives with Chemotherapy through Traditional Knowledge and Modern AdvancesView all 20 articles
A network pharmacology approach and experimental validation to investigate the anticancer mechanism of diosgenin against esophageal cancer via PI3K/Akt pathway
Provisionally accepted
Jiajia Bi1*Jia Wei1
Hui Zhang1Jianhui Kang1Yifan Dong1Yiming Xie1Sujuan Chen1Shuangping Ma1Zihan Zhao1Ruifei Wang2
Qingxiang Yang2- 1Xinxiang Medical University, Xinxiang, China
- 2Henan Normal University, Xinxiang, China
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Background: Esophageal cancer (ESCA) is a prevalent malignant cancer within the digestive system, ranking among the most aggressive cancers worldwide. It is a leading cause of cancer-related deaths. Diosgenin, a natural steroidal saponin and a bioactive constituent of yam, has shown efficacy in inhibiting various cancer cells and inducing programmed cell death. Methods: The potential targets and core targets of diosgenin against ESCA were collected through bioinformatics screening. Gene set variation analysis (GSVA) was performed to evaluate the expression of these core targets in ESCA tissues. Functional enrichment analysis and molecular docking were performed for the core targets. The specific mechanism of diosgenin against ESCA was verified via in vivo and in vitro experiments. Results: In all, 136 potential targets of action and 10 core targets were screened. The core targets were highly expressed in ESCA. They play roles in ESCA cell apoptosis, cell cycle, and PI3K/AKT pathway. The experimental results showed that diosgenin could induce ESCA cell cycle arrest at the G0/G1 phase and lead to apoptosis by inhibiting the PI3K/AKT pathway. Conclusion: Our results revealed that diosgenin induces the apoptosis of ESCA cells through the PI3K signaling pathway, as predicted by network pharmacology analysis. Our findings provide new mechanistic insights into the therapeutic potential of diosgenin and support its development as a natural product-based agent for ESCA treatment.
Keywords: Network Pharmacology, Diosgenin, esophageal cancer, PI3K/AKT/mTOR, Apoptosis
Received: 17 Jun 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Bi, Wei, Zhang, Kang, Dong, Xie, Chen, Ma, Zhao, Wang and Yang. 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: Jiajia Bi, Xinxiang Medical University, Xinxiang, 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.