Involvement of mitogen-activated protein kinases and p21Waf1 in hydroxyurea-induced G1 arrest and senescence of McA-RH7777 rat hepatoma cell line

• Published in: Experimental & molecular medicine pp. 493 - 498
• Main Authors: 홍승희, 홍범식, 김대철, 노미숙, 박주인, 하소희, 전호순, 정진숙
• Format: Journal Article
• Language: Korean
• Published: 생화학분자생물학회 01.10.2004
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

Hydroxyurea is comonly used to treat he-matologic disorders and some type of solid tumors, but the mechanism for its therapeutic efect is not clearly known. In this study, we examined the effect of hydroxyurea on rat he-patoma McA-RH7 cells, specifically, on the role of mitogen-activated protein (MAP) kinase signal transduction pathways and p21Waf1, p27Kip1 treated with hydroxyurea for 7 days, caused the inhibition of cel 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-β-gal-actosidase staining, and cels arrest at G1 phase of cel cycle. Phosphorylation of MAP kinases, such as ERK, JNK, and p38, was found to be decreased after treatment of cels with hydroxyurea. But, the expresion of p21Waf1 was increased, while p27Kip1 and p53 were not de-tected in hydroxyurea treated rat hepatoma cells. Hydroxyurea treatment induced G1 arest and a senescence-like changes in rat hepatoma McA-RH7777 cels may be the likely results of signal disruption of MAP kinases (ERK, JNK, and p38 MAP kinase) and p21Waf1 over-expression. KCI Citation Count: 6