Document Detail

Opposing securin and p53 protein expression in the oxaliplatin-induced cytotoxicity of human colorectal cancer cells.
MedLine Citation:
PMID:  17045763     Owner:  NLM     Status:  MEDLINE    
Oxaliplatin, a clinical anticancer drug, has been used to treat colorectal cancer. Securin and p53 have been shown to regulate the cell cycle arrest and apoptosis. However, roles of securin and p53 on the oxaliplatin-induced cytotoxicity in human colorectal cancer cells remain unclear. Treatment with 1-10 microM oxaliplatin for 24 h induced the cell death, growth inhibition, and cell cycle arrest in RKO colorectal carcinoma cells. The phospho-p53 (Ser-15), total p53, and p21 proteins were elevated by oxaliplatin in RKO cells; conversely, oxaliplatin decreased the securin protein expression. The p53-functional RKO cells were higher on the cytotoxicity and cell cycle arrest at the G1 and G2/M phases than the p53-mutational SW480 cells after treatment with oxaliplatin. Oxaliplatin inhibited the securin protein expression in the p53-functional cells but not in the p53-mutational cells. The securin-wild type cells were more sensitive than the securin-null cells on the increases of cytotoxicity and sub-G1 fractions following treatment with oxaliplatin. Nevertheless, oxaliplatin elevated the activation of p53 in both securin-wild type and securin-null cells. As a whole, it is the first time to demonstrate that oxaliplatin inhibits the securin protein expression via a p53-dependent pathway, and p53 and securin may modulate the oxaliplatin-induced cytotoxicity in human colorectal cancer cells.
Shu-Jun Chiu; Tzu-Sheng Hsu; Jui-I Chao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-15
Journal Detail:
Title:  Toxicology letters     Volume:  167     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-22     Completed Date:  2007-01-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  122-30     Citation Subset:  IM    
Molecular Anticancer Laboratory, Institute of Pharmacology and Toxicology, College of Life Sciences, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 970, Taiwan.
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MeSH Terms
Antineoplastic Agents / toxicity*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Colorectal Neoplasms / metabolism*
Neoplasm Proteins / metabolism*
Organoplatinum Compounds / toxicity*
Tumor Suppressor Protein p53 / metabolism*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Neoplasm Proteins; 0/Organoplatinum Compounds; 0/Tumor Suppressor Protein p53; 0/pituitary tumor-transforming proteins; 63121-00-6/oxaliplatin

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