Role of p21CIP1 as a determinant of SC-560 response in human HCT116 colon carcinoma cells.
- Author:
Eunmyong LEE
1
;
Moon Kyung CHOI
;
Inn Oc HAN
;
Soo Jeong LIM
Author Information
1. Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea. sjlim@sejong.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
caspase;
cell cycle;
cyclin-dependent kinase inhibitor p21;
growth inhibitors;
HCT116 cells;
SC 560
- MeSH:
Reactive Oxygen Species/metabolism;
Pyrazoles/*pharmacology;
Mutation;
Immunoblotting;
Humans;
HCT116 Cells;
Genotype;
Flow Cytometry;
Dose-Response Relationship, Drug;
Cyclooxygenase Inhibitors/pharmacology;
Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism/*physiology;
Colonic Neoplasms/genetics/metabolism/pathology;
Cell Survival/drug effects;
Cell Proliferation/drug effects;
Cell Differentiation/drug effects;
Cell Cycle Proteins/metabolism;
Cell Cycle/drug effects;
Apoptosis/drug effects;
Antineoplastic Agents/pharmacology
- From:Experimental & Molecular Medicine
2006;38(3):325-331
- CountryRepublic of Korea
- Language:English
-
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.
