ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Ethacrynic acid and a derivative enhance apoptosis in arsenic trioxide-treated myeloid leukemia and lymphoma cells: the role of glutathione S-transferase p1-1.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- A phase II study of arsenic trioxide in patients with relapsed or refractory malignant lymphoma.Medical oncology (Northwood, London, England) · 2015Trial
- Ethacrynic Oxadiazole 6u Induces Apoptosis by Targeting mTOR/c-Flip Axis and Noxa in Lymphoma Cells.Biological procedures online · 2026Article
- Combination of Ethacrynic Acid and ATRA Triggers Differentiation and/or Apoptosis of Acute Myeloid Leukemia Cells through ROS.Anti-cancer agents in medicinal chemistry · 2024Article
- Research progress on arsenic, arsenic-containing medicinal materials, and arsenic-containing preparations: clinical application, pharmacological effects, and toxicity.Frontiers in pharmacology · 2024Review
- Ethacrynic Acid: A Promising Candidate for Drug Repurposing as an Anticancer Agent.International journal of molecular sciences · 2023Review
- Ethacrynic acid and cinnamic acid combination exhibits selective anticancer effects on K562 chronic myeloid leukemia cells.Molecular biology reports · 2022Article
- Ethacrynic Acid Enhances the Antitumor Effects of Afatinib in EGFR/T790M-Mutated NSCLC by Inhibiting WNT/Beta-Catenin Pathway Activation.Disease markers · 2021Article
- Identification of glutathione S-transferase π 1 as a prognostic proteomic biomarker for multiple myeloma using proteomic profiling.Oncology letters · 2020Article
- New insights into redox homeostasis as a therapeutic target in B-cell malignancies.Current opinion in hematology · 2017Review
- Wnt signaling pathway protein LEF1 in cancer, as a biomarker for prognosis and a target for treatment.American journal of cancer research · 2017Review
- Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer.Oncotarget · 2016Article
- High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia and may be targeted by ethacrynic acid.Oncotarget · 2016Article
- Sorafenib Inhibition of Mcl-1 Accelerates ATRA-Induced Apoptosis in Differentiation-Responsive AML Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- The Flavonoid 7,4'-Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion via Regulation of NF-κB, STAT6, and HDAC2.Phytotherapy research : PTR · 2015Article
- Dihydroartemisinin and its derivative induce apoptosis in acute myeloid leukemia through Noxa-mediated pathway requiring iron and endoperoxide moiety.Oncotarget · 2015Article
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- Effects of arsenic sulfide (AsBiomedical reports · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeArsenic trioxide (ATO) as a single agent is used for treatment of acute promyelocytic leukemia (APL) with minimal toxicity, but therapeutic effect of ATO in other types of malignancies has not been achieved. We tested whether a combination with ethacrynic acid (EA), a glutathione S-transferase P1-1 (GSTP1-1) inhibitor, and a reactive oxygen species (ROS) inducer will extend the therapeutic effect of ATO beyond APL. EXPERIMENTAL
designThe combined apoptotic effects of ATO plus ethacrynic acid were tested in non-APL leukemia and lymphoma cell lines. The role of ROS, GSTP1-1, glutathione (GSH), and Mcl-1 in apoptosis was determined. The selective response to this combination of cells with and without GSTP1-1 expression was compared.
resultsATO/EA combination synergistically induced apoptosis in myeloid leukemia and lymphoma cells. This treatment produced high ROS levels, activated c-jun-NH(2)-kinase (JNK), and reduced Mcl-1 protein. This led to the decrease of mitochondrial transmembrane potential, release of cytochrome c, and subsequently, to activation of caspase-3 and -9. Induction of apoptosis in leukemia and lymphoma cells expressing GSTP1-1 required high ethacrynic acid concentrations to be combined with ATO. Silencing of GSTP1 in leukemia cells sensitized them to ATO/EA-induced apoptosis. In a subgroup of B-cell lymphoma, which does not express GSTP1-1, lower concentrations of ethacrynic acid and its more potent derivative, ethacrynic acid butyl-ester (EABE), decreased intracellular GSH levels and synergistically induced apoptosis when combined with ATO.
conclusionB-cell lymphoma cells lacking GSTP1-1 are more sensitive than myeloid leukemia cells to ATO/EA-induced apoptosis.
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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.