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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Regulating SLC7A11/GSH/GPX4 axis by glucose dyshomeostasis to simultaneously promote disulfidptosis, cuproptosis and

Mengsi Zhang1,2, Hao Zheng3, Hao Jin3

  • 1Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, 130021, PR China.

Bioactive Materials
|November 21, 2025
PubMed

Insights

Disrupting glucose metabolism via glucose dyshomeostasis triggers multiple cell death types, including disulfidptosis, cuproptosis, and ferroptosis. This approach enhances ovarian tumor therapy by targeting the SLC7A11/GSH/GPX4 antioxidant axis.

Area of Science:

  • Biomedical Engineering
  • Oncology
  • Metabolic Therapy

Background:

  • Glucose dyshomeostasis is a key target in tumor metabolic therapy, potentially overcoming resistance to regulated cell deaths (RCDs).
  • The precise pathways linking glucose metabolism disruption to RCDs and their therapeutic applications require further elucidation.
  • The SLC7A11/GSH/GPX4 antioxidant axis is implicated in cellular responses to metabolic stress.

Purpose of the Study:

  • To investigate how glucose dyshomeostasis impacts the SLC7A11/GSH/GPX4 antioxidant axis.
  • To explore the potential of simultaneously inducing disulfidptosis, cuproptosis, and ferroptosis through glucose dyshomeostasis.
  • To evaluate the therapeutic efficacy of a novel nanoshuttle system in ovarian tumor models.

Main Methods:

  • Utilized glucose oxidase (GOx)-modified copper-apigenin (CuAp) network nanoshuttles (CuAp@GOx NSs) to induce glucose dyshomeostasis.
  • Inhibited glucose transporter 1 (GLUT1) and consumed glucose to achieve dyshomeostasis.
  • Assessed the impact on NADPH levels, the SLC7A11/GSH/GPX4 axis, and subsequent RCD induction.

Main Results:

  • Glucose dyshomeostasis downregulated NADPH, disrupting the SLC7A11/GSH/GPX4 antioxidant axis.
  • Simultaneous induction of disulfidptosis (via cystine accumulation), cuproptosis (via GSH-mediated copper inactivation), and ferroptosis (via GPX4 downregulation) was achieved.
  • CuAp@GOx NSs demonstrated significant efficacy in an ovarian tumor model due to the combined RCD effects.

Conclusions:

  • Glucose dyshomeostasis effectively targets the SLC7A11/GSH/GPX4 axis to induce multiple RCDs.
  • CuAp@GOx NSs offer a promising therapeutic strategy for ovarian cancer by combining disulfidptosis, cuproptosis, and ferroptosis.
  • This study presents a novel approach for tumor therapy centered on manipulating glucose metabolism and RCD pathways.
Keywords:
CuproptosisDisulfidptosisFerroptosisGlucose metabolismSLC7A11/GSH/GPX4 axis

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