Synthesis, characterization and augmented anticancer potential of PEG-betulinic acid conjugate.
Mater Sci Eng C Mater Biol Appl
; 73: 616-626, 2017 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-28183653
ABSTRACT
Betulinic acid (BA), a pentacyclic lupine-type triterpene, is reported to inhibit cell growth in a variety of cancers. However, its efficacy is limited by its poor aqueous solubility and relatively short half-life. In this study, BA-monomethoxy polyethylene glycol (mPEG) conjugate was synthesized by covalent coupling the C-28 carboxylic acid position of BA with amine groups of mPEG, in order to improve its solubility and anticancer efficacy. mPEG-BA conjugate was characterized using various analytical techniques including NMR, FT-IR and MALDI-MS. The mPEG-BA conjugate was cytotoxic, demonstrated internalization and induced cell apoptosis in Hep3B and Huh7 hepatic cancer cells. The western-blot analysis revealed, marked decrease in Bcl-2/Bax ratio, and increase in cleaved-PARP and cleaved-caspase-3 expressions. In vivo studies in Ehrlich ascites tumor (EAT) model following intravenous administration demonstrated significant reduction in tumor volume in case of PEGylated BA as compare to native BA. Furthermore, PEGylated BA treated EAT mice showed no biochemical and histological toxicities. These findings demonstrate the potential of PEGylated BA in cancer therapy, with improved water solubility and efficacy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
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Triterpenos
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Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mater Sci Eng C Mater Biol Appl
Año:
2017
Tipo del documento:
Article
País de afiliación:
India