ArticleMolecular pharmacology2013
Overexpression of Mcl-1 confers multidrug resistance, whereas topoisomerase IIβ downregulation introduces mitoxantrone-specific drug resistance in acute myeloid leukemia.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- ETV6 Rearrangement Suppresses CDKN1B Transcription by Disrupting an Intragenic Super-enhancer in Acute Lymphoblastic Leukemia.Cancer research · 2026Article
- Mitochondrial integrated stress response activation creates a therapeutic vulnerability to MCL-1 inhibition in acute myeloid leukemia.Cell death & disease · 2026Article
- The Protective Effects of Mcl-1 on Mitochondrial Damage and Oxidative Stress in Imiquimod-Induced Cancer Cell Death.Cancers · 2024Article
- Use of CRISPR/Cas9 with Homology-Directed Repair to Gene-Edit Topoisomerase IIThe Journal of pharmacology and experimental therapeutics · 2024Article
- Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma.Oral oncology · 2023Article
- Effects of hsa-miR-9-3p and hsa-miR-9-5p on Topoisomerase IIThe Journal of pharmacology and experimental therapeutics · 2023Article
- Three-Component Synthesis of 2-Amino-3-cyano-4Pharmaceuticals (Basel, Switzerland) · 2021Article
- Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence PharmacokineticsACS omega · 2021Article
- miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1.Frontiers in cell and developmental biology · 2021Article
- Article
- Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance.Molecular cancer · 2020Review
- Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer.Breast cancer research and treatment · 2019Article
- Renieramycin T Induces Lung Cancer Cell Apoptosis by Targeting Mcl-1 Degradation: A New Insight in the Mechanism of Action.Marine drugs · 2019Article
- Sodium butyrate and panobinostat induce apoptosis of chronic myeloid leukemia cells via multiple pathways.Molecular genetics & genomic medicine · 2019Article
- In-silico comparison of two induction regimens (7 + 3 vs 7 + 3 plus additional bone marrow evaluation) in acute myeloid leukemia treatment.BMC systems biology · 2019Article
- Histone Deacetylase Inhibitor Enhances the Efficacy of MEK Inhibitor through NOXA-Mediated MCL1 Degradation in Triple-Negative and Inflammatory Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells.Blood cancer journal · 2017Article
- microRNAs and Acute Myeloid Leukemia Chemoresistance: A Mechanistic Overview.Frontiers in oncology · 2017Review
- Dual NAMPT and BTK Targeting Leads to Synergistic Killing of Waldenström Macroglobulinemia Cells Regardless of MYD88 and CXCR4 Somatic Mutation Status.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Impact of Anthocyanidins on Mitoxantrone-Induced Cytotoxicity and Genotoxicity: An In Vitro and In Vivo Analysis.Integrative cancer therapies · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Drug resistance is a serious challenge in cancer treatment and can be acquired through multiple mechanisms. These molecular changes may introduce varied extents of resistance to different therapies and need to be characterized for optimal therapy choice. A recently discovered small molecule, ethyl-2-amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate) (CXL017), reveals selective cytotoxicity toward drug-resistant leukemia. A drug-resistant acute myeloid leukemia cell line, HL60/MX2, also failed to acquire resistance to CXL017 upon chronic exposure and regained sensitivity toward standard therapies. In this study, we investigated the mechanisms responsible for HL60/MX2 cells' drug resistance and the molecular basis for its resensitization. Results show that the HL60/MX2 cell line has an elevated level of Mcl-1 protein relative to the parental cell line, HL60, and its resensitized cell line, HL60/MX2/CXL017, whereas it has a reduced level of topoisomerase IIβ. Mcl-1 overexpression in HL60/MX2 cells is mainly regulated through phospho-extracellular signal-regulated protein kinases 1 and 2-mediated Mcl-1 stabilization, whereas the reduction of topoisomerase IIβ in HL60/MX2 cells is controlled through genetic downregulation. Upregulating Mcl-1 introduces multidrug resistance to standard therapies, whereas its downregulation results in significant cell death. Downregulating topoisomerase IIβ confers resistance specifically to mitoxantrone, not to other topoisomerase II inhibitors. Overall, these data suggest that Mcl-1 overexpression is a critical determinant for cross-resistance to standard therapies, whereas topoisomerase IIβ downregulation is specific to mitoxantrone resistance.
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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.