ArticleInternational journal of molecular sciences2021
Mebendazole Mediates Proteasomal Degradation of GLI Transcription Factors in Acute Myeloid Leukemia.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- MCL1 inhibition to enhance the efficacy of MYB targeting in pediatric acute myeloid leukemia.Cell death & disease · 2026Article
- Mebendazole Shows Antiproliferative and Antimigratory Effects in Paediatric Low-Grade Glioma Models.Oncology research · 2026Article
- Downregulation of S6 Kinase and Hedgehog-Gli1 by Inhibition of Fatty Acid Synthase in AML with FLT3-ITD Mutation.International journal of molecular sciences · 2025Article
- GLI2 inhibits cisplatin sensitivity in gastric cancer through DEC1/ZEB1 mediated EMT.Cell death & disease · 2025Article
- Mebendazole effectively overcomes imatinib resistance by dual-targeting BCR/ABL oncoprotein and β-tubulin in chronic myeloid leukemia cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Review
- MYB as a Critical Transcription Factor and Potential Therapeutic Target in AML.Advances in experimental medicine and biology · 2024Review
- High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The prognosis of elderly AML patients is still poor due to chemotherapy resistance. The Hedgehog (HH) pathway is important for leukemic transformation because of aberrant activation of GLI transcription factors. MBZ is a well-tolerated anthelmintic that exhibits strong antitumor effects. Herein, we show that MBZ induced strong, dose-dependent anti-leukemic effects on AML cells, including the sensitization of AML cells to chemotherapy with cytarabine. MBZ strongly reduced intracellular protein levels of GLI1/GLI2 transcription factors. Consequently, MBZ reduced the GLI promoter activity as observed in luciferase-based reporter assays in AML cell lines. Further analysis revealed that MBZ mediates its anti-leukemic effects by promoting the proteasomal degradation of GLI transcription factors via inhibition of HSP70/90 chaperone activity. Extensive molecular dynamics simulations were performed on the MBZ-HSP90 complex, showing a stable binding interaction at the ATP binding site. Importantly, two patients with refractory AML were treated with MBZ in an off-label setting and MBZ effectively reduced the GLI signaling activity in a modified plasma inhibitory assay, resulting in a decrease in peripheral blood blast counts in one patient. Our data prove that MBZ is an effective GLI inhibitor that should be evaluated in combination to conventional chemotherapy in the clinical setting.
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Registered trials
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