ArticleCancers2020
xCT Inhibition Increases Sensitivity to Vorinostat in a ROS-Dependent Manner.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Circular RNAs in ferroptosis regulation and tumor progression of gynecological and breast cancers: molecular mechanisms and therapeutic potential.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- STY12, a Novel NQO1/HDAC Dual-Targeting Agent, Exhibits Potent Anti-Pancreatic Cancer Activity by ROS-Mediated DNA Damage.Biomolecules · 2026Article
- FSP1 and histone deacetylases suppress cancer persister cell ferroptosis.Science advances · 2026Article
- Targeting Ferroptosis to Overcome Drug Resistance in Cancer: Molecular Mechanisms and Therapeutic Prospects.Biomolecules & therapeutics · 2026Review
- Epigenetic modifications in ferroptosis regulation of breast cancer.American journal of cancer research · 2026Review
- Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment.Molecular cancer · 2025Review
- Epigenetic regulation of targeted ferroptosis: A new strategy for drug development.Journal of pharmaceutical analysis · 2024Review
- Research Progress on the Mechanism of Histone Deacetylases in Ferroptosis of Glioma.Oncology reviews · 2024Review
- Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.Journal of cellular and molecular medicine · 2024Review
- Review
- Repurposing of neprilysin inhibitor 'sacubitrilat' as an anti-cancer drug by modulating epigenetic and apoptotic regulators.Scientific reports · 2023Article
- SelSA-1, a novel HDAC inhibitor demonstrates enhanced chemotherapeutic potential by redox modulation.Scientific reports · 2023Article
- Role of ferroptosis in colorectal cancer.World journal of gastrointestinal oncology · 2023Review
- First-in-Class Dual Mechanism Ferroptosis-HDAC Inhibitor Hybrids.Journal of medicinal chemistry · 2022Article
- Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology: Progress and updates.World journal of gastrointestinal oncology · 2022Review
- Glutamine metabolism in cancers: Targeting the oxidative homeostasis.Frontiers in oncology · 2022Review
- System XFrontiers in pharmacology · 2022Review
- Emerging Potential Therapeutic Targets of Ferroptosis in Skeletal Diseases.Oxidative medicine and cellular longevity · 2022Review
- Development and Verification of a Prognostic Ferroptosis-Related Gene Model in Triple-Negative Breast Cancer.Frontiers in oncology · 2022Article
- Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer.Cancers · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
As histone deacetylase inhibitors (HDACIs) have limited efficacy against solid tumors, we investigated whether and how oxidative stress is involved in sensitivity to HDACIs to develop a novel therapeutic option of HDACIs treatment. We first tested whether a reduction of the antioxidant glutathione (GSH) by glutamine deprivation affects sensitivity to a commercially available HDACI vorinostat and reactive oxygen species (ROS) accumulation. Next we investigated the relationship between a glutamate-cystine transporter xCT and the efficacy of vorinostat using siRNA of xCT and bioinformatic analyses. Finally, we verified the combinatory effects of vorinostat and the xCT inhibitor salazosulfapyridine (SASP) on ROS accumulation, cell death induction, and colony formation. Glutamine deprivation increased vorinostat-mediated cell death with ROS accumulation. Genetic ablation of xCT improved the efficacy of vorinostat, consistent with the results of public data analyses demonstrating that xCT expressions positively correlate with insensitivity to HDACIs in many types of cancer cell lines. Vorinostat caused ROS accumulation when combined with SASP, possibly resulting in synergistic ferroptosis. Our study provides a novel mechanistic insight into the mechanism underlying sensitivity to HDACIs involving xCT, suggesting xCT to be a promising predictive marker of HDACIs and rationalizing combinatory therapy of HDACIs with xCT inhibitors to induce ferroptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.