Abstract | BACKGROUND: METHODS: NOD/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. RESULTS: HF 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. CONCLUSION: Taken together, our results demonstrate that HF inhibits SMAD2 signaling and reduces leukemia growth and angiogenesis.
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Authors | Patricia A Assis, Lorena L De Figueiredo-Pontes, Ana Silvia G Lima, Vitor Leão, Larissa A Cândido, Carolina T Pintão, Aglair B Garcia, Fabiano P Saggioro, Rodrigo A Panepucci, Fernando Chahud, Arnon Nagler, Roberto P Falcão, Eduardo M Rego |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 34
Pg. 65
(Jun 23 2015)
ISSN: 1756-9966 [Electronic] England |
PMID | 26099922
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Piperidines
- Quinazolinones
- SMAD2 protein, human
- Smad2 Protein
- halofuginone
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Topics |
- Animals
- Disease Models, Animal
- Humans
- Immunophenotyping
- Leukemia, Promyelocytic, Acute
(metabolism)
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Mice, Transgenic
- Neovascularization, Pathologic
- Phosphorylation
- Piperidines
(metabolism)
- Quinazolinones
(metabolism)
- Smad2 Protein
(genetics, metabolism)
- Tumor Cells, Cultured
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