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SarCNU‐induced G 2 /M arrest in hepatoma cells is mediated by a p53‐independent phosphorylation of cdc‐2 at Tyr15
Author(s) -
Hung Huynh,
Pierce Chow Kad Hoe,
Chee Soo Khee,
Lawrence Panasci,
Hung Nguyen Thanh
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20336
Subject(s) - phosphorylation , microbiology and biotechnology , chemistry , p53 protein , biology , apoptosis , biochemistry
Hepatocellular carcinoma (HCC) is a major health problem in the Asia‐Pacific region, with high incidence and mortality rate. There is currently no effective treatment for inoperable cases that represent the vast majority of patients. In the present study, we report that in vitro treatment of primary hepatoma, HepG2 (wild‐type p53), PLC/PRF/5 (p53‐mutant), and Hep3B (p53‐deleted) cells with 2‐chloroethyl‐3‐sarcosinamide‐1‐nitrosourea (SarCNU) resulted in upregulation of p53, p21 Cip1/Waf1 , phosphorylated cdc‐2 at Tyr15 in wild‐type p53 cells and phosphorylation of cdc‐2 at Tyr15 in p53‐mutant or p53‐deleted hepatoma cells. This was accompanied by the reduction in cdc‐2 kinase activity and G 2 /M cell cycle arrest. These findings indicate that SarCNU‐induced G 2 /M growth arrest in hepatoma cells by a p53‐independent phosphorylation of cdc‐2. Our data suggest the potential use of SarCNU in treatment of HCC. © 2005 Wiley‐ Liss, Inc.