ArticleLeukemia2008
Effective killing of Gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated mechanism.
Article in Leukemia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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.
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Who cites it
50 citing papers in PubMed, 96 citations in OpenAlex.
- No evident dose-response relationship between cellular ROS level and its cytotoxicity--a paradoxical issue in ROS-based cancer therapy.Scientific reports · 2014Trial
- Physiological Significance and Functions of AA.Reviews of physiology, biochemistry and pharmacology · 2027Review
- Isothiocyanates as Multi-Target Natural Compounds in Leukemia: Mechanisms, Selectivity, and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Natural Products Targeting BCR-ABL: A Plant-Based Approach to Chronic Myeloid Leukemia Treatment.Molecules (Basel, Switzerland) · 2025Review
- Targeting ROS in cancer: rationale and strategies.Nature reviews. Drug discovery · 2024Review
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- Modulation of energy metabolism to overcome drug resistance in chronic myeloid leukemia cells through induction of autophagy.Cell death discovery · 2022Article
- Ferroptosis: At the Crossroad of Gemcitabine Resistance and Tumorigenesis in Pancreatic Cancer.International journal of molecular sciences · 2021Review
- Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy.Cell death & disease · 2020Review
- Relationship of oxidative stress in the resistance to imatinib in Tunisian patients with chronic myeloid leukemia: A retrospective study.Journal of clinical laboratory analysis · 2020Article
- Benzyl isothiocyanate inhibits invasion and induces apoptosis via reducing S100A4 expression and increases PUMA expression in oral squamous cell carcinoma cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2019Article
- Hematopoietic Stem Cells: Normal Versus Malignant.Antioxidants & redox signaling · 2018Review
- Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers.Molecules (Basel, Switzerland) · 2018Review
- Discovering proteasomal deubiquitinating enzyme inhibitors for cancer therapy: lessons from rational design, nature and old drug reposition.Future medicinal chemistry · 2018Review
- Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side.Journal of experimental & clinical cancer research : CR · 2018Review
- Mitochondrial dysfunction in cancer chemoprevention by phytochemicals from dietary and medicinal plants.Seminars in cancer biology · 2017Review
- Identification of deubiquitinase targets of isothiocyanates using SILAC-assisted quantitative mass spectrometry.Oncotarget · 2017Article
- Inhibition of cancer antioxidant defense by natural compounds.Oncotarget · 2017Review
- DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity.AIMS genetics · 2017Review
- Optimal ROS Signaling Is Critical for Nuclear Reprogramming.Cell reports · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Mutation of Bcr-Abl is an important mechanism by which chronic myelogenous leukemia (CML) cells become resistant to Gleevec. The T315I mutation is clinically significant since CML cells harboring this mutation are insensitive to Gleevec and other Bcr-Abl-targeted drugs. Identification of new agents capable of effectively killing CML cells with T315I mutation would have important therapeutic implications in Gleevec-resistant CML. Here, we showed that beta-phenylethyl isothiocyanate (PEITC), a natural compound found in vegetables, is effective in killing CML cells expressing T315I BCR-ABL. Treatment of leukemia cell lines harboring wild-type or mutant Bcr-Abl with 10 microM PEITC resulted in an elevated ROS stress and a redox-mediated degradation of the BCR-ABL protein, leading to massive death of the leukemia cells. Antioxidant NAC attenuated the PEITC-induced oxidative stress in CML cells and prevented the degradation of BCR-ABL, caspase-3 activation and cell death. We further showed that the ROS-induced degradation of BCR-ABL was mediated partially by caspase-3 and the proteasome pathway. The ability of PEITC to effectively kill T315I-positive CML cells was further confirmed using primary leukemia cells isolated from CML patients. Our results suggest that PEITC is a promising compound capable of killing Gleevec-resistant CML cells through a ROS-mediated mechanism and warrants further investigations.
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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.