Mammea E/BB, an isoprenylated dihydroxycoumarin protonophore that potently uncouples mitochondrial electron transport, disrupts hypoxic signaling in tumor cells.
J Nat Prod
; 73(11): 1868-72, 2010 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-20929261
ABSTRACT
The mammea-type coumarin mammea E/BB (1) was found to inhibit both hypoxia-induced and iron chelator-induced hypoxia-inducible factor-1 (HIF-1) activation in human breast tumor T47D cells with IC(50) values of 0.96 and 0.89 µM, respectively. Compound 1 suppressed the hypoxic induction of secreted VEGF protein (T47D cells) and inhibited cell viability/proliferation in four human tumor cell lines. Compound 1 (at 5 and 20 µM) inhibited human breast tumor MDA-MB-231 cell migration. While the mechanisms that underlie their biological activities have remained unknown, prenylated mammea coumarins have been shown to be cytotoxic to human tumor cells, suppress tumor growth in animal models, and display a wide variety of antimicrobial effects. Mechanistic studies revealed that 1 appears to exert an assemblage of cellular effects by functioning as an anionic protonophore that potently uncouples mitochondrial electron transport and disrupts mitochondrial signaling in human tumor cell lines.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cumarínicos
/
Casca de Planta
/
Mammea
/
Fator 1 Induzível por Hipóxia
/
Mitocôndrias
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
País/Região como assunto:
Caribe
/
Caribe ingles
/
Dominica
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos