ArticleAntioxidants & redox signaling2011
Inhibition of mitochondrial respiration and rapid depletion of mitochondrial glutathione by β-phenethyl isothiocyanate: mechanisms for anti-leukemia activity.
Article in Antioxidants & redox signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
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- Marrow leptin-LEPR signaling rewires mitochondrial oxidative metabolism to confer chemoresistance in acute myeloid leukemia.Cell death & disease · 2026Article
- NDUFS3 promotes proliferation via glucose metabolism reprogramming inducing AMPK phosphorylating PRPS1 to increase the purine nucleotide synthesis in melanoma.Cell death and differentiation · 2025Article
- Mitochondrial transport of glutathione in diabetic retinopathy.Free radical biology & medicine · 2025Article
- Current Insights into Glutathione Depletion in Adult Septic Patients.Antioxidants (Basel, Switzerland) · 2025Review
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
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- Use of Drug Sensitisers to Improve Therapeutic Index in Cancer.Pharmaceutics · 2024Review
- Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation.International journal of molecular sciences · 2024Review
- Type 2 Diabetes Related Mitochondrial Defects in Peripheral Mononucleated Blood Cells from Overweight Postmenopausal Women.Biomedicines · 2023Article
- Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer.Oxidative medicine and cellular longevity · 2022Review
- Dopamine and Methamphetamine Differentially Affect Electron Transport Chain Complexes and Parkin in Rat Striatum: New Insight into Methamphetamine Neurotoxicity.International journal of molecular sciences · 2021Article
- Mitochondrial iron-sulfur clusters: Structure, function, and an emerging role in vascular biology.Redox biology · 2021Review
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- Glutathione Metabolism and the Novel Role of Mitochondrial GSH in Retinal Degeneration.Antioxidants (Basel, Switzerland) · 2021Review
- An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells.Antioxidants (Basel, Switzerland) · 2021Article
- FGF, Mechanism of Action, Role in Parkinson's Disease, and Therapeutics.Frontiers in pharmacology · 2021Review
- PEITC triggers multiple forms of cell death by GSH-iron-ROS regulation in K7M2 murine osteosarcoma cells.Acta pharmacologica Sinica · 2020Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsβ-Phenethyl isothiocyanate (PEITC) is a natural product with potent anticancer activity against human leukemia cells including drug-resistant primary leukemia cells from patients. This study aimed at investigating the key mechanisms that contribute to the potent anti-leukemia activity of PEITC and at evaluating its therapeutic potential.
resultsOur study showed that PEITC caused a rapid depletion of mitochondrial glutathione (GSH) and a significant elevation of reactive oxygen species (ROS) and nitric oxide, and induced a disruption of the mitochondrial electron transport complex I manifested by an early degradation of NADH dehydrogenase Fe-S protein-3 and a significant suppression of mitochondrial respiration. Using biochemical and pharmacological approaches, we further showed that inhibition of mitochondrial respiration alone by rotenone caused only a moderate cytotoxicity in leukemia cells, whereas a combination of respiratory inhibition and an ROS-generating agent exhibited a synergistic effect against leukemia and lymphoma cells. INNOVATION AND
conclusionAlthough PEITC is a reactive compound and might have multiple mechanisms of action, we showed that a rapid depletion of GSH and inhibition of mitochondrial respiration are two important early events that induced synergistic cytotoxicity in leukemia cells. These findings not only suggest that PEITC is a promising compound for potential use in leukemia treatment, but also provide a basis for developing new therapeutic strategies to effectively kill leukemia cells by using a novel combination to modulate ROS and inhibit mitochondrial respiration.
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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.