Radiosensitizing activity of a novel Benzoxazine through the promotion of apoptosis and inhibition of DNA repair.
Invest New Drugs
; 32(3): 424-35, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24627282
ABSTRACT
The DNA dependant protein kinase (DNA-PK) enzyme plays a major part in the repair of double stranded breaks induced by radiation and hence in the radio-resistance of tumour cells. Inhibitors of DNA-PK have been tested successfully in the past for their ability to sensitize cancer cells to the effects of radiation. Here we present a novel benzoxazine, 8-methyl-2-(morpholine-4yl)-7-(pyridine-3-methoxy)-4H-1,3-benzoxacine-4-one (LTU27) and analyse its ability to cause sensitization of lung cancer and colon cancer cells to radiation. There was a significant reduction in survival rate, increase in apoptosis and inhibition in autophosphorylation of DNA-PK and AKT1 after treating them concomitantly with both radiation and LTU27. The mechanism of action appears to be through inhibition of DNA-PK leading to delayed DNA repair and promotion of apoptosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
/
Morfolinas
/
Benzoxazinas
/
Proteína Quinase Ativada por DNA
Limite:
Humans
Idioma:
En
Revista:
Invest New Drugs
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Austrália