ArticleCell death & disease2018
Vorinostat and quinacrine have synergistic effects in T-cell acute lymphoblastic leukemia through reactive oxygen species increase and mitophagy inhibition.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- The mitochondria as an emerging target of self-renewal in T-cell acute lymphoblastic leukemia.Cancer biology & therapy · 2025Review
- SSRP1/SLC3A2 Axis in Arginine Transport: A New Target for Overcoming Immune Evasion and Tumor Progression in Peripheral T-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities.Stem cell research & therapy · 2025Review
- ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs.Nature communications · 2023Article
- Autophagy in Hematological Malignancies.Cancers · 2022Review
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?Antioxidants (Basel, Switzerland) · 2022Review
- Novel histone deacetylase inhibitor CT-101 induces γ-globin gene expression in sickle erythroid progenitors with targeted epigenetic effects.Blood cells, molecules & diseases · 2022Article
- Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention.Drug discovery today · 2022Review
- Adipocyte-mediated epigenomic instability in human T-ALL cells is cytotoxic and phenocopied by epigenetic-modifying drugs.Frontiers in cell and developmental biology · 2022Article
- Quinacrine-CASIN combination overcomes chemoresistance in human acute lymphoid leukemia.Nature communications · 2021Article
- Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses.Antioxidants (Basel, Switzerland) · 2021Review
- Therapeutic Interaction of Apatinib and Chidamide in T-Cell Acute Lymphoblastic Leukemia through Interference with Mitochondria Associated Biogenesis and Intrinsic Apoptosis.Journal of personalized medicine · 2021Article
- Article
- Review
- Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities.Cells · 2021Review
- Recent Advances in Molecular Diagnosis and Prognosis of Childhood B Cell Lineage Acute Lymphoblastic Leukemia (B-ALL).Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2021Review
- Quinacrine inhibits GSTA1 activity and induces apoptosis through GOncotarget · 2020Article
- Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy.Cell death & disease · 2020Review
- Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia.BioMed research international · 2020Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration. Compared to the single treatment, QC plus vorinostat significantly induced apoptosis, disrupted the mitochondrial transmembrane potential, and decreased Mcl-1 and Bcl-2/Bax ratio. Interestingly, the application of QC plus vorinostat resulted in mitophagy blockade, as reflected by the increase in the K63-linked ubiquitination of mitochondria protein and the formation of mitochondrial aggresomes. QC plus vorinostat markedly increased the reactive oxygen species (ROS) level in cells. Moreover, the ROS scavenger N-acetylcysteine (NAC) abrogated QC plus vorinostat-induced ROS, decreased the ubiquitination of mitochondria proteins, and cell death. Finally, using a xenograft mouse model, we demonstrated that QC plus vorinostat significantly reduced cell proliferation and induced cell death in vivo. Taken together, our results showed that the combination of QC with vorinostat may represent a novel regimen for the treatment of T-cell acute lymphoblastic leukemia, which deserves clinical evaluation in the future.
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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.