Role of p21CIP1 as a determinant of SC-560 response in human HCT116 colon carcinoma cells
Experimental & Molecular Medicine
;
: 325-331, 2006.
Artículo
en Inglés
| WPRIM
| ID: wpr-51256
ABSTRACT
SC-560, a strucutral analogue of celecoxib, induces growth inhibition in a wide range of human cancer cells in a cyclooxygenase (COX)-independent manner. Since SC-560 suppresses the growth of cancer cells mainly by inducing cell cycle arrest, we sought to examine the role of p21CIP1, a cell cycle regulator protein, in the cellular response against SC-560 by using p21(+/+)and p21(-/-)isogenic HCT116 colon carcinoma cells. In HCT116 (p21(+/+)) cells, SC-560 dose-dependently induced growth inhibition and cell cycle arrest at the G1 phase without significant apoptosis induction. SC-560-induced cell cycle arrest was accompanied by upregulation of p21CIP1. However, the extent of SC-560-induced accumulation at the G1 phase was approximately equal in the p21(+/+)and the p21(-/-)cells. Nonetheless, the growth inhibition by SC-560 was increased in p21(-/-)cells than p21(+/+)cells. SC-560-induced reactive oxygen species (ROS) generation did not differ between p21(+/+)and p21(-/-)cells but the subsequent activaton of apoptotic caspase cascade was more pronounced in p21(-/-)cells compared with p21(+/+)cells. These results suggest that p21CIP1 blocks the SC-560-induced apoptotic response of HCT116 cells. SC-560 combined with other therapy that can block p21 CIP1 expression or function may contribute to the effective treatment of colon cancer.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Pirazoles
/
Immunoblotting
/
Ciclo Celular
/
Diferenciación Celular
/
Supervivencia Celular
/
Inhibidores de la Ciclooxigenasa
/
Especies Reactivas de Oxígeno
/
Apoptosis
/
Neoplasias del Colon
/
Proteínas de Ciclo Celular
Límite:
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2006
Tipo del documento:
Artículo
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