ArticleCancer biology & therapy2016
HIF-1α inhibition by 2-methoxyestradiol induces cell death via activation of the mitochondrial apoptotic pathway in acute myeloid leukemia.
Article in Cancer biology & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- TIMM23 overexpression drives NSCLC cell growth and survival by enhancing mitochondrial function.Cell death & disease · 2025Article
- The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.Cancer cell international · 2024Article
- Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.Clinical epigenetics · 2023Review
- The Normobaric Oxygen Paradox-Hyperoxic Hypoxic Paradox: A Novel Expedient Strategy in Hematopoiesis Clinical Issues.International journal of molecular sciences · 2022Review
- The genesis and evolution of acute myeloid leukemia stem cells in the microenvironment: From biology to therapeutic targeting.Cell death discovery · 2022Review
- Self-Nanoemulsifying Drug Delivery System of 2-Methoxyestradiol Exhibits Enhanced Anti-Proliferative and Pro-Apoptotic Activities in MCF-7 Breast Cancer Cells.Life (Basel, Switzerland) · 2022Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Transcriptional Regulation of Yin-Yang 1 Expression through the Hypoxia Inducible Factor-1 in Pediatric Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Article
- Combined Effects of 2-Methoxyestradiol (Hypoxia-Inducible Factor 1Journal of immunology research · 2022Article
- Simvastatin regulates the proliferation, apoptosis, migration and invasion of human acute myeloid leukemia cells via miR-19a-3p/HIF-1α axis.Bioengineered · 2021Article
- Evaluation of 2-methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma.Molecular and clinical oncology · 2021Article
- Oxidative Stress and ROS-Mediated Signaling in Leukemia: Novel Promising Perspectives to Eradicate Chemoresistant Cells in Myeloid Leukemia.International journal of molecular sciences · 2021Review
- The crosstalk between HIFs and mitochondrial dysfunctions in cancer development.Cell death & disease · 2021Review
- Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy.Cell death & disease · 2020Review
- SIRT3 deacetylase activity confers chemoresistance in AML via regulation of mitochondrial oxidative phosphorylation.British journal of haematology · 2019Article
- 2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90.Journal of oncology · 2019Article
- Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines.Drug design, development and therapy · 2018Article
- 2-Methoxyestradiol Attenuates Testosterone-Induced Benign Prostate Hyperplasia in Rats through Inhibition of HIF-1Oxidative medicine and cellular longevity · 2018Article
- The hypoxia signalling pathway in haematological malignancies.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bone marrow microenvironment plays an important role in the development and progression of AML. Leukemia stem cells are in a hypoxic condition, which induces the expression of HIF-1α. Aberrant activation of HIF-1α is implicated in the poor prognosis of patients with acute myeloid leukemia (AML). Herein, we investigated the expression of HIF-1α in AML and tested 2-methoxyestradiol (2ME2) as a candidate HIF-1α inhibitor for the treatment of AML. We found that HIF-1α was overexpressed in AML. HIF-1α suppression by 2ME2 significantly induced apoptosis of AML cells, and it outperformed traditional chemotherapy drugs such as cytarabine. At the same time, 2ME2 downregulated the transcriptional levels of VEGF, GLUT1 and HO-1 in cellular assays. Additionally, 2ME2 displayed antileukemia activity in bone marrow blasts from AML patients, but showed little effect on normal cells. 2ME2-induced activation of mitochondrial apoptotic pathway is mediated by reactive oxygen species (ROS), which decreased the slight effect of drug on normal cells. Our data show that supression of HIF-1α expression significantly reduced the survival of AML cell lines, suggesting that 2ME2 may represent a powerful therapeutic approach for patients with AML.
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