Investigation of the anti-angiogenesis effects induced by deoxypodophyllotoxin-5-FU conjugate C069 against HUVE cells.
Bioorg Med Chem Lett
; 27(4): 713-717, 2017 02 15.
Article
em En
| MEDLINE
| ID: mdl-28129979
ABSTRACT
We have found that the deoxypodophyllotoxin-5-fluorouracil conjugate, 4'-O-demethyl-4-deoxyppodophyllotoxin-4'-yl 4-((6-(2-(5-fluorouracil-yl)acetamido) hexyl)amino)-4-oxobutanoate (C069), possessed superior cytotoxicities and less toxicity compared with etoposide. In this paper, the anti-angiogenic and vascular disrupting activities of C069 were examined with several in vitro and in vivo models. First, we demonstrated that C069 significantly inhibited the proliferation, migration, tube formation and disrupted the formed tube-like structures of HUVE cells, and inhibited angiogenesis in chicken chorioallantoic membrane assay. Furthermore, we found that C069 inhibited tube formation of HUVE cells by down-regulating the MMP-2, MMP-9, and phosphorylation of Akt and ß-catenin. These results provided the initial evidence that C069 exerts potent anti-angiogenic and vascular disrupting effects.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Podofilotoxina
/
Neovascularização Fisiológica
/
Inibidores da Angiogênese
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Proliferação de Células
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Fluoruracila
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2017
Tipo de documento:
Article