ArticleAntioxidants (Basel, Switzerland)2021
PKCα Inhibition as a Strategy to Sensitize Neuroblastoma Stem Cells to Etoposide by Stimulating Ferroptosis.
Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Significance of GSH and HRedox report : communications in free radical research · 2026Review
- DMAMCL induces ferroptosis in neuroblastoma by targeting HMOX1 in MYCN-amplified subtypes whereas targeting STEAP3 in MYCN-nonamplified subtypes.Redox report : communications in free radical research · 2026Article
- Insulin production in the retina drives autocrine signalling and metabolism reprogramming of the ARPE-19, a retinal pigment epithelium cellular model.Cellular and molecular life sciences : CMLS · 2026Article
- Beyond readthrough: ataluren restores mitochondrial function and reduces oxidative stress in FANCA-mutated cells via mTOR-DRP1 modulation.Cell death discovery · 2026Article
- The investigational anti-B7-H3 antibody-drug conjugate vobramitamab duocarmazine exerts anti-tumor activity in vitro and in vivo in pediatric sarcoma preclinical models.Cell death & disease · 2026Article
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity.Journal of translational internal medicine · 2025Article
- Unlocking ferroptosis to overcome cancer stem cells-mediated treatment failure and immune evasion.Frontiers in immunology · 2025Review
- Evaluation of In Vitro Biological Activity of Flavanone/Chromanone Derivatives: Molecular Analysis of Anticancer Mechanisms in Colorectal Cancer.International journal of molecular sciences · 2024Article
- Iron metabolism: backfire of cancer cell stemness and therapeutic modalities.Cancer cell international · 2024Review
- Article
- Cisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect.Cancers · 2024Article
- Metabolism-regulated ferroptosis in cancer progression and therapy.Cell death & disease · 2024Review
- Glutathione and Xanthine Metabolic Changes in Tamoxifen Resistant Breast Cancer Cell Lines are Mediated by Down-Regulation ofJournal of Cancer · 2024Article
- PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis.Antioxidants (Basel, Switzerland) · 2023Article
- Regulation of iron metabolism and ferroptosis in cancer stem cells.Frontiers in oncology · 2023Review
- PLX4032 resistance of patient-derived melanoma cells: crucial role of oxidative metabolism.Frontiers in oncology · 2023Article
- Integrative analysis of multi-omics data for discovery of ferroptosis-related gene signature predicting immune activity in neuroblastoma.Frontiers in pharmacology · 2023Article
- Review
- Hormesis and Oxidative Distress: Pathophysiology of Reactive Oxygen Species and the Open Question of Antioxidant Modulation and Supplementation.Antioxidants (Basel, Switzerland) · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) are a limited cell population inside a tumor bulk characterized by high levels of glutathione (GSH), the most important antioxidant thiol of which cysteine is the limiting amino acid for GSH biosynthesis. In fact, CSCs over-express xCT, a cystine transporter stabilized on cell membrane through interaction with CD44, a stemness marker whose expression is modulated by protein kinase Cα (PKCα). Since many chemotherapeutic drugs, such as Etoposide, exert their cytotoxic action by increasing reactive oxygen species (ROS) production, the presence of high antioxidant defenses confers to CSCs a crucial role in chemoresistance. In this study, Etoposide-sensitive and -resistant neuroblastoma CSCs were chronically treated with Etoposide, given alone or in combination with Sulfasalazine (SSZ) or with an inhibitor of PKCα (C2-4), which target xCT directly or indirectly, respectively. Both combined approaches are able to sensitize CSCs to Etoposide by decreasing intracellular GSH levels, inducing a metabolic switch from OXPHOS to aerobic glycolysis, down-regulating glutathione-peroxidase-4 activity and stimulating lipid peroxidation, thus leading to ferroptosis. Our results suggest, for the first time, that PKCα inhibition inducing ferroptosis might be a useful strategy with which to fight CSC chemoresistance.
Indexed as
Identifiers
What OpenQuestion holds
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.