Antiangiogenic and apoptotic properties of a novel amphiphilic folate-heparin-lithocholate derivative having cellular internality for cancer therapy.
Pharm Res
; 24(4): 705-14, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17318418
ABSTRACT
PURPOSE:
Anitangiogenic and apoptotic properties of a novel chemically modified heparin derivative with low anticoagulant activity were evaluated on the experimental in vitro and in vivo model. MATERIALS ANDMETHODS:
Heparin-lithocholate conjugate (HL) was initially synthesized by covalently bonding lithocholate to heparin. Folate-HL conjugate (FHL) was further synthesized by conjugating folate to HL. Antiangiogenic and apoptotic abilities of HL and FHL were characterized in vitro and in vivo experimentations.RESULTS:
Compared to unmodified heparin, both HL and FHL represented a low anticoagulant activity (38 and 28%, respectively). HL and FHL maintained antiangiogenic activity even further modification from the results of Matrigel plugs assay. FHL specifically induced apoptosis on KB cells having highly expressed folate receptor after cellular internalization. Both administered HL and FHL had similar antiangiogenic activity and inhibitory effect on tumor growth in vivo although FHL induced higher apoptosis on tumor tissues.CONCLUSIONS:
In vivo tumor growth inhibition was possibly due to the decrease of vessel density and apoptotic cell death, although antiangiogenic effect of FHL seemed more actively affected on growth inhibition than apoptotic potential in vivo system. Thus, Low anticoagulant FHL having antiangiogenic and apoptotic properties would provide benefits for the development of a new class of anticancer agent.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Heparina
/
Apoptose
/
Inibidores da Angiogênese
/
Ácido Litocólico
/
Neoplasias Experimentais
/
Neovascularização Patológica
/
Antineoplásicos
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2007
Tipo de documento:
Article