ArticleOncotarget2016
Interconnections between apoptotic and autophagic pathways during thiopurine-induced toxicity in cancer cells: the role of reactive oxygen species.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Population frequencies of thiopurine-related pharmacogenes in healthy individuals from Kosovo.Human genome variation · 2026Article
- Characterisation of autophagy induction by the thiopurine drugs azathioprine, mercaptopurine and thioguanine in THP-1 macrophages.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Article
- Apoptin mediates mitophagy and endogenous apoptosis by regulating the level of ROS in hepatocellular carcinoma.Cell communication and signaling : CCS · 2022Article
- Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?Antioxidants (Basel, Switzerland) · 2022Review
- Grb2 interacts with necrosome components and is involved in rasfonin-induced necroptosis.Cell death discovery · 2022Article
- Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities.Cells · 2021Review
- Apoptin Regulates Apoptosis and Autophagy by Modulating Reactive Oxygen Species (ROS) Levels in Human Liver Cancer Cells.Frontiers in oncology · 2020Article
- Azathioprine Has a Deleterious Effect on the Bone Health of Mice with DSS-Induced Inflammatory Bowel Disease.International journal of molecular sciences · 2019Article
- Purine-Metabolising Enzymes and Apoptosis in Cancer.Cancers · 2019Review
- Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelialDisease models & mechanisms · 2019Article
- 6-Thioguanine and Its Analogs Promote Apoptosis of Castration-Resistant Prostate Cancer Cells in a BRCA2-Dependent Manner.Cancers · 2019Article
- Corilagin inhibits breast cancer growth via reactive oxygen species-dependent apoptosis and autophagy.Journal of cellular and molecular medicine · 2018Article
- Diverse Inhibitors of De Novo Purine Synthesis Promote AICAR-Induced AMPK Activation and Glucose Uptake in L6 Myotubes.BioFactors (Oxford, England)Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are a class of genotoxic drugs extensively used in the treatment of various illnesses including leukemia. Their underlying molecular mechanism of action involves the activation of apoptosis and autophagy but remains widely unclear. Here we present evidence that autophagy induction by thiopurines is a survival mechanism that antagonizes apoptosis and is involved in degrading damaged mitochondria through mitophagy. On the other hand, apoptosis is the main cell death mechanism by thiopurines as its inhibition prohibited cell death. Thus a tight interplay between apoptosis and autophagy controls cell fate in response to thiopurine treatment. Moreover, thiopurines disrupt mitochondrial function and induce a loss of the mitochondrial transmembrane potential. The involvement of the mitochondrial pathway in thiopurine-induced apoptosis was further confirmed by increased formation of reactive oxygen species (ROS). Inhibiting oxidative stress protected the cells from thiopurine-induced cell death and ROS scavenging prohibited autophagy induction by thiopurines. Our data indicate that the anticarcinogenic effects of thiopurines are mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis and autophagy.
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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.