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Examine how RRx-001 induces disulfidptosis via NADPH dysregulation and its role in triggering immunogenic cell death in hepatocellular carcinoma.

March 28, 2026Cell Death DiscoveryOpen Access

RRx-001 inhibits G6PD to deplete NADPH and trigger disulfidptosis coupled with DAMP-mediated immunogenic cell death in hepatocellular carcinoma

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Investigates RRx-001's effects on disulfidptosis and immune activation in hepatocellular carcinoma, suggesting therapeutic potential.

Examine how RRx-001 induces disulfidptosis via NADPH dysregulation and its role in triggering immunogenic cell death in hepatocellular carcinoma.
Used Huh-7 and Hepa1-6 HCC cell lines and a murine xenograft model
Assessed drug effects through CCK-8, flow cytometry, transmission electron microscopy
Analyzed metabolic parameters and protein expression via immunofluorescence and Western blotting
Studied immune microenvironment changes using transcriptomic sequencing and immunohistochemistry
RRx-001 reduced NADPH by downregulating G6PD, causing redox imbalance and F-actin contraction
Treatment increased DAMPs release, confirming immunogenic cell death
In vivo, RRx-001 significantly suppressed tumor growth and enhanced T cell infiltration
Transcriptomic analysis indicated improved antitumor immunity pathways

Huang et al. (2026) studied this question.

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