ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicNew Advancement in Tumor Microenvironment Remodeling and Cancer Therapy, Volume IIView all 10 articles
The effect of Disulfidptosis induced by glucose starvation in SLC7A11high Ovarian Cancer
Provisionally accepted
- The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
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Abstract Objective: Disulfidptosis is a glucose deprivation-induced cell death mechanism driven by disulfide stress-mediated actin cytoskeleton disintegration[1]. This study explored whether SLC7A11high ovarian cancer (OC) undergoes disulfidptosis under conditions of glucose starvation. This study aimed to provide a new treatment option for OC. Methods: Initially, we assay to assess the cell viability of IOSE 80 and OVCAR 3 under conditions of glucose sufficiency and starvation. Subsequently, we examine the difference in SLC7A11 expression between the two cell types under the specified conditions. The intracellular NADP+/NADPH ratio and oxidized glutathione disulfide / reduced glutathione (GSSG/GSH) ratio were quantified using the test kit. And the effect of SLC7A11 on cell death by using SLC7A11 transporter activity inhibitors. Cell counting kit-8 (CCK-8) was used to investigate the effect of intracellular disulfide bond levels on cell death due to glucose starvation. At last, we investigated the effect of reactive oxygen species (ROS) on the cell death. Results: The results revealed that the SLC7A11 expression level in OVCAR 3 was higher than that in IOSE 80, and it exhibited a lower tolerance to glucose starvation. Glucose starvation stimulates SLC7A11 expression in OVCAR 3 cells, and SLC7A11 facilitates cell death in OC cells under conditions of glucose starvation. Elevated disulfide bond levels in ovarian cancer cells promote cell death under glucose starvation conditions.The NADP+/NADPH ratio and the GSSG/GSH ratio increased in OVCAR 3 cells under conditions of glucose starvation. The cell death of OVCAR 3 cells under conditions of glucose starvation was unrelated to the ROS level increase. Conclusions: Glucose starvation induces high SLC7A11 expression in OC cells, resulting in cell death. This type of cell death is associated with NADPH depletion in the cell and the accumulation of disulfides. Therefore, it is considered that disulfidptosis may occur in SLC7A11high OC cells under glucose starvation conditions.
Keywords: ovarian cancer, disulfidptosis, SLC7A11, Glucose starvation, disulfide bond
Received: 08 Apr 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 Chen, Ou and SHI. 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: Wen-Jing SHI, swj3647@163.com
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