Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis.
Glycobiology
; 16(3): 210-20, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16282605
ABSTRACT
Galectins, a family of structurally related carbohydrate-binding proteins, contribute to different events associated with cancer biology, including apoptosis, homotypic cell aggregation, angiogenesis and tumor-immune escape. To interfere with galectin-carbohydrate interactions during tumor progression, a current challenge is the design of specific galectin inhibitors for therapeutic purposes. Here, we report the synthesis of three novel low molecular weight synthetic lactulose amines (SLA) (1) N-lactulose-octamethylenediamine (LDO), (2) N,N'-dilactulose-octamethylenediamine (D-LDO), and (3) N,N'-dilactulose-dodecamethylenediamine (D-LDD). These compounds showed a differential ability to inhibit binding of galectin-1 and/or galectin-3 to the highly glycosylated protein 90K in solid-phase assays. In addition, each compound demonstrated selective regulatory effects in different events linked to tumor progression including tumor-cell apoptosis, homotypic cell aggregation, and endothelial cell morphogenesis. Our results suggest that galectin inhibitors with subtle differences in their carbohydrate structures may be potentially used to specifically block different steps of tumor growth and metastasis.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Galectinas
/
Células Endoteliais
/
Aminas
/
Lactulose
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article