ArticleJournal of experimental & clinical cancer research : CR2015
Halofuginone inhibits phosphorylation of SMAD-2 reducing angiogenesis and leukemia burden in an acute promyelocytic leukemia mouse model.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation.Oncogene · 2025Article
- Prognostic significance of angiogenesis-associated molecules and Immunologic characteristic in elderly patients with acute myeloid leukemia.Annals of hematology · 2025Article
- Review
- Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway.Scientific reports · 2025Article
- Novel Products as Promising Therapeutic Agents for Angiogenesis Inhibition.Current drug delivery · 2025Review
- Halofuginone prevents outer retinal degeneration in a mouse model of light-induced retinopathy.PloS one · 2024Article
- Control of fibrosis with enhanced safety via asymmetric inhibition of prolyl-tRNA synthetase 1.EMBO molecular medicine · 2023Article
- EPRS1 Controls the TGF-Molecular and cellular biology · 2023Article
- Targeting the integrated stress response in hematologic malignancies.Experimental hematology & oncology · 2022Review
- Effects of corticosteroids vs halofuginone on vocal fold wound healing in an ovine model.Laryngoscope investigative otolaryngology · 2021Article
- Natural Products: A Promising Therapeutics for Targeting Tumor Angiogenesis.Frontiers in oncology · 2021Review
- Halofuginone inhibits tumorigenic progression of 5-FU-resistant human colorectal cancer HCT-15/FU cells by targeting miR-132-3pOncology letters · 2020Article
- 7‑Difluoromethyl‑5,4'‑dimethoxygenistein exerts anti‑angiogenic effects on acute promyelocytic leukemia HL‑60 cells by inhibiting the TLR4/NF‑κB signaling pathway.Molecular medicine reports · 2020Article
- Proline Metabolism in Tumor Growth and Metastatic Progression.Frontiers in oncology · 2020Review
- Antiangiogenic Effect of Alkaloids.Oxidative medicine and cellular longevity · 2019Review
- Stent-Jailing Technique Reduces Aneurysm Recurrence More Than Stent-Jack Technique by Causing Less Mechanical Forces and Angiogenesis and Inhibiting TGF-β/Smad2,3,4 Signaling Pathway in Intracranial Aneurysm Patients.Frontiers in physiology · 2018Article
- Identification of RSK and TTK as Modulators of Blood Vessel Morphogenesis Using an Embryonic Stem Cell-Based Vascular Differentiation Assay.Stem cell reports · 2016Article
- PML-RAR alpha induces the downmodulation of HHEX: a key event responsible for the induction of an angiogenetic response.Journal of hematology & oncology · 2016Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHalofuginone (HF) is a low-molecular-weight alkaloid that has been demonstrated to interfere with Metalloproteinase-2 (MMP-2) and Tumor Growth Factor-β (TGF-β) function and, to present antiangiogenic, antiproliferative and proapoptotic properties in several solid tumor models. Based on the fact that high levels of Vascular Endothelial Growth Factor (VEGF) and increased angiogenesis have been described in acute myeloid leukemia and associated with disease progression, we studied the in vivo effects of HF using an Acute Promyelocytic Leukemia (APL) mouse model.
methodsNOD/SCID mice were transplanted with leukemic cells from hCG-PML/RARA transgenic mice (TM) and treated with HF 150 μg/kg/day for 21 days. The leukemic infiltration and the percentage of VEGF+ cells were evaluated by morphology and flow cytometry. The effect of HF on the gene expression of several pro- and antiangiogenic factors, phosphorylation of SMAD2 and VEGF secretion was assessed in vitro using NB4 and HUVEC cells.
resultsHF treatment resulted in hematological remission with decreased accumulation of immature cell and lower amounts of VEGF in BM of leukemic mice. In vitro, HF modulated gene expression of several pro- and antiangiogenic factors, reduced VEGF secretion and phosphorylation of SMAD2, blocking TGF-β-signaling.
conclusionTaken together, our results demonstrate that HF inhibits SMAD2 signaling and reduces leukemia growth and angiogenesis.
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