G-quadruplex-binding benzo[a]phenoxazines down-regulate c-KIT expression in human gastric carcinoma cells.
J Am Chem Soc
; 133(8): 2658-63, 2011 Mar 02.
Article
en En
| MEDLINE
| ID: mdl-21294544
ABSTRACT
There is considerable interest in the structure and function of G-quadruplex nucleic acid secondary structures, their cellular functions, and their potential as therapeutic targets. G-Quadruplex sequence motifs are prevalent in gene promoter regions and it has been hypothesized that G-quadruplex structure formation is associated with the transcriptional status of the downstream gene. Using a functional cell-based assay, we have identified two novel G-quadruplex ligands that reduce the transcription of a luciferase reporter driven from the G-quadruplex-containing c-KIT promoter. We have further shown that endogenous c-KIT expression in a human gastric carcinoma cell line is also reduced on treatment with these molecules. Biophysical analysis using surface plasmon resonance has shown that these molecules preferentially bind with high affinity to one of the two G-quadruplex sequences in the c-KIT promoter over double-stranded DNA. This work highlights the utility of cell-based reporter assays to identify new G-quadruplex binding molecules that modulate transcription and identifies benzo[a]phenoxazine derivatives as potential antitumor agents.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oxazinas
/
Neoplasias Gástricas
/
Regulación hacia Abajo
/
Regulación Neoplásica de la Expresión Génica
/
Proteínas Proto-Oncogénicas c-kit
/
G-Cuádruplex
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2011
Tipo del documento:
Article
País de afiliación:
Reino Unido