Involvement of mitogen-activated protein kinases and p21Waf1 in hydroxyurea-induced G1 arrest and senescence of McA-RH7777 rat hepatoma cell line.
- Author:
Seung Hee HONG
1
;
Bum Sik HONG
;
Dae Cheol KIM
;
Mee Sook RHO
;
Joo In PARK
;
Soe Hee RHA
;
Ho Sun JUN
;
Jin Sook JEONG
Author Information
1. Division of Basic Science, National Cancer Center Research Institute, Goyang, Gyeonggi 411-769, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
hydroxyurea;
MAP kinases;
p21Waf1;
rat hepatoma cells
- MeSH:
Animals;
Antineoplastic Agents/*pharmacology;
Cell Aging/drug effects;
Cell Cycle Proteins/analysis/metabolism/*physiology;
Cell Line, Tumor;
Cell Proliferation/drug effects;
G1 Phase/drug effects/physiology;
Hydroxyurea/*pharmacology;
Liver Neoplasms, Experimental/enzymology/*metabolism;
Mitogen-Activated Protein Kinases/analysis/*physiology;
Phosphorylation/drug effects;
Protein p53/analysis/metabolism;
Rats;
Research Support, Non-U.S. Gov't;
Tumor Suppressor Proteins/analysis/metabolism;
Up-Regulation
- From:Experimental & Molecular Medicine
2004;36(5):493-498
- CountryRepublic of Korea
- Language:English
-
Abstract:
Hydroxyurea is commonly used to treat hematologic disorders and some type of solid tumors, but the mechanism for its therapeutic effect is not clearly known. In this study, we examined the effect of hydroxyurea on rat hepatoma McA-RH7777 cells, specifically, on the role of mitogen-activated protein (MAP) kinase signal transduction pathways and p21Waf1, p27Kip1 and p53. Rat hepatoma McA-RH7777 cells treated with hydroxyurea for 7 days, caused the inhibition of cell growth in a dose-dependent manner. But, this growth inhibition was not caused by necrosis or apoptosis but instead was associated with cell senescence-like change as evidenced by senescence associated-beta-galactosidase staining, and cells arrest at G1 phase of cell cycle. Phosphorylation of MAP kinases, such as ERK, JNK, and p38, was found to be decreased after treatment of cells with hydroxyurea. But, the expression of p21Waf1 was increased, while p27Kip1 and p53 were not detected in hydroxyurea treated rat hepatoma cells. Hydroxyurea treatment induced G1 arrest and a senescence-like changes in rat hepatoma McA-RH7777 cells may be the likely results of signal disruption of MAP kinases (ERK, JNK, and p38 MAP kinase) and p21Waf1 over-expression.
