ArticlePloS one2011
Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Discovery of novel quinazoline derivatives containing trifluoromethyl against cell proliferation by targeting werner helicase.Molecular diversity · 2026Article
- Review
- Translating molecular insights into clinical success: alkaloid-based therapies for leukemia.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- New uses of halofuginone to treat cancer.Journal of pharmaceutical analysis · 2025Review
- The Therapeutic Effects of Bioactive Compounds on Colorectal Cancer via PI3K/Akt/mTOR Signaling Pathway: A Critical Review.Food science & nutrition · 2024Review
- Marine derived macrolide bryostatin 4 inhibits the TGF-β signaling pathway against acute erythroleukemia.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Halofuginone, a promising drug for treatment of pulmonary hypertension.British journal of pharmacology · 2021Article
- Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells.International journal of nanomedicine · 2021Article
- Halofuginone inhibits tumorigenic progression of 5-FU-resistant human colorectal cancer HCT-15/FU cells by targeting miR-132-3pOncology letters · 2020Article
- Proline Metabolism in Tumor Growth and Metastatic Progression.Frontiers in oncology · 2020Review
- Ubiquitin enzymes in the regulation of immune responses.Critical reviews in biochemistry and molecular biology · 2017Review
- Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.Human reproduction (Oxford, England) · 2016Article
- Halofuginone inhibits colorectal cancer growth through suppression of Akt/mTORC1 signaling and glucose metabolism.Oncotarget · 2015Article
- Halofuginone inhibits phosphorylation of SMAD-2 reducing angiogenesis and leukemia burden in an acute promyelocytic leukemia mouse model.Journal of experimental & clinical cancer research : CR · 2015Article
- Anticancer activity of halofuginone in a preclinical model of osteosarcoma: inhibition of tumor growth and lung metastases.Oncotarget · 2015Article
- Halofuginone - the multifaceted molecule.Molecules (Basel, Switzerland) · 2015Review
- Effect of halofuginone on the inhibition of proliferation and invasion of hepatocellular carcinoma HepG2 cell line.International journal of clinical and experimental pathology · 2015Article
- Article
- Plant-derived anticancer agents: a promising treatment for bone metastasis.BoneKEy reports · 2014Review
- Synthetic phosphoethanolamine has in vitro and in vivo anti-leukemia effects.British journal of cancer · 2013Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) expression in acute promyelocytic leukemia (APL) impairs transforming growth factor beta (TGFβ) signaling, leading to cell growth advantage. Halofuginone (HF), a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice subjected to transplantation with leukemic cells from human chorionic gonadotrophin-PML-RARα transgenic mice (TG). Cell cycle analysis using incorporated bromodeoxyuridine and 7-amino-actinomycin D showed that, in NB4 and NB4-R2 APL cell lines, HF inhibited cellular proliferation (P<0.001) and induced apoptosis (P = 0.002) after a 24-hour incubation. Addition of TGFβ revealed that NB4 cells were resistant to its growth-suppressive effects and that HF induced these effects in the presence or absence of the cytokine. Cell growth inhibition was associated with up-regulation of TGFβ target genes involved in cell cycle regulation (TGFB, TGFBRI, SMAD3, p15, and p21) and down-regulation of MYC. Additionally, TGFβ protein levels were decreased in leukemic TG animals and HF in vivo could restore TGFβ values to normal. To test the in vivo anti-leukemic activity of HF, we transplanted NOD/SCID mice with TG leukemic cells and treated them with HF for 21 days. HF induced partial hematological remission in the peripheral blood, bone marrow, and spleen. Together, these results suggest that HF has anti-proliferative and anti-leukemic effects by reversing the TGFβ blockade in APL. Since loss of the TGFβ response in leukemic cells may be an important second oncogenic hit, modulation of TGFβ signaling may be of therapeutic interest.
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