AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025360379
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ORIGINAL RESEARCH ARTICLE

Sulforaphane selectively inhibits glucose metabolism in PIK3CA-mutated ovarian cancer cells

Zijiao Li1† ,  Yinli Su2† ,  Liying Qin3 ,  Han Wu1 ,  Wan Fu1 ,  Xinyu Wang1 ,  Longyang Li1 ,  Xuerou Wang1 ,  Di Chen4* ,  Ya Xie1* ,  Linlin Li3*
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1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
2 Department of Obstetrics and Gynecology, Fuyang Municipal People’s Hospital, Fuyang, Anhui, China
3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
4 Department of Pharmacology, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
†These authors contributed equally to this work.
EJMO, 025360379 https://doi.org/10.36922/EJMO025360379
Received: 4 September 2025 | Revised: 25 September 2025 | Accepted: 9 October 2025 | Published online: 12 December 2025
(This article belongs to the Special Issue Tumor Immune Microenvironment and Intervention Strategies)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: PIK3CA mutations are prevalent in ovarian cancer (OC) and drive cancer progression by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Sulforaphane (SFN), a natural compound derived from cruciferous vegetables, exhibits antitumor effects; however, its specific mechanisms, especially those related to metabolic reprogramming in PIK3CA-mutated cancers, remain unclear.

Objective: This study investigates the alterations in glucose metabolism and the selective inhibitory effects of SFN in PIK3CA-mutated OC cells.

Methods: Clinical samples from OC patients were analyzed to determine PIK3CA mutation status and its prognostic relevance to patient outcome. PIK3CA-mutated and wild-type OC cell lines were used for in vitro analysis. Glycolysis and mitochondrial respiration were assessed using the Seahorse XF Analyzer. Gene and protein expression were analyzed through RNA sequencing, real-time quantitative polymerase chain reaction, and Western blotting. Metabolite levels were m-easured through untargeted mass spectrometry. The effects of SFN were validated in vitro and in a mouse xenograft model.

Results: PIK3CA mutations were associated with poorer progression-free survival in OC patients. PIK3CA-mutated OC cells exhibited enhanced glycolysis and tricarboxylic acid (TCA) cycle activity compared to wild-type cells. SFN selectively inhibited the proliferation of PIK3CA-mutated cells by suppressing glycolysis and the TCA cycle, downregulating key glycolytic enzymes (e.g., hexokinase 1 and 2) and reducing TCA cycle intermediates (e.g., α-ketoglutaric acid and citrate). Mechanistically, SFN inhibited the PI3K/Akt pathway, resulting in reduced Akt phosphorylation. In vivo, SFN more effectively inhibited tumor growth in mice bearing PIK3CA-mutated xenografts.

Conclusion: PIK3CA mutations enhance both glycolysis and the TCA cycle in OC. SFN selectively inhibits the growth of PIK3CA-mutated OC cells by targeting the PI3K/Akt pathway, leading to the suppression of glucose metabolism. These findings highlight the therapeutic potential of SFN for PIK3CA-mutated OC.

Keywords
PIK3CA mutation
Ovarian cancer
Glucose metabolism
Funding
This study was funded by the Natural Science Foundation of Henan (242300421273), the Beijing Science and Technology Innovation Medical Development Foundation (KC2021-JX-0186-130), the CSCO-Zai Ding Cancer Treatment Research Fund project (Y-zai2022/ms-0246), the National Outstanding Youth Science Fund Project of the National Natural Science Foundation of China, (81802770), and the Henan Provincial Health and Health Commission, Joint Co-construction Project of Medical Science and Technology Tackling Program in Henan Province (2018020056).
Conflict of interest
The authors declare no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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