Synthetic, non-saccharide, glycosaminoglycan mimetics selectively target colon cancer stem cells.
ACS Chem Biol
; 9(8): 1826-33, 2014 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-24968014
ABSTRACT
Selective targeting of cancer stem-like cells (CSCs) is a paradigm-shifting approach. We hypothesized that CSCs can be targeted by interfering with functions of sulfated glycosaminoglycans, which play key roles in cancer cell growth, invasion and metastasis. We developed a tandem, dual screen strategy involving (1) assessing inhibition of monolayer versus spheroid growth and (2) assessing inhibition of primary versus secondary spheroid growth to identify G2.2, a unique sulfated nonsaccharide GAG mimetic (NSGM) from a focused library of 53 molecules, as a selective inhibitor of colon CSCs. The NSGM down-regulated several CSC markers through regulation of gene transcription, while closely related, inactive NSGMs G1.4 and G4.1 demonstrated no such changes. G2.2's effects on CSCs were mediated, in part, through induction of apoptosis and inhibition of self-renewal factors. Overall, this work presents the proof-of-principle that CSCs can be selectively targeted through novel NSGMs, which are likely to advance fundamental understanding on CSCs while also aiding development of novel therapeutic agents.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Colon_e_reto
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Neoplasias do Colo
/
Mimetismo Molecular
/
Glicosaminoglicanos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos