Document Detail


5-fluorouracil mediates apoptosis and G1/S arrest in laryngeal squamous cell carcinoma via a p53-independent pathway.
MedLine Citation:
PMID:  17207318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent in the treatment of laryngeal squamous cell carcinoma. 5-FU can induce cell cycle arrest or apoptosis in various cancers via either a p53-dependent or a p53-independent pathway; however, its pathway of action in laryngeal carcinoma is unknown. In this study, we aim to investigate the role that p53 plays in the cytotoxic effect of 5-FU on laryngeal squamous carcinoma cells. MATERIALS AND METHODS: We employed two human laryngeal squamous carcinoma cell lines with different p53 statuses-one (UMSCC12) had truncated non-functional p53 and the other (UMSCC11A) had mutant but functional p53. Cell death was detected using cytotoxicity assay and Annexin V staining. Cell cycles were analyzed by flow cytometry. Western blot was used to analyze the protein expression. RESULTS: 5-FU induces apoptosis in both UMSCC12 and UMSCC11A cells in a dose- and time-dependent manner, suggesting that the pathway was p53-independent. 5-FU induced the accumulation of retinoblastoma protein and a cyclin dependent kinase inhibitor, p21WAF1/CIP1, in both UMSCC12 and UMSCC11A cells. However, 5-FU did not induce p53 expression in either UMSCC12 or UMSCC11A cells. In addition, G1/S cell cycle phase arrest was associated with antiproliferative activity of 5-FU in both cell lines. In order to gain an insight into the role p53 plays in response to 5-FU treatment in laryngeal carcinoma, we further transfected either a wildtype p53 plasmid or an empty pcDNA3.1 vector into UMSCC12 cells. We found that 5-FU increased pRb and p21WAF1/CIP1 expression in both p53-transfected and vector-transfected cells without the significant accumulation of p53. DISCUSSION: Our results suggest that 5-FU mediates apoptosis and G1/S cell cycle phase arrest in laryngeal carcinoma via a p53-independent but p21WAF1/CIP1-dependent or p21WAF1/CIP1-Rb-dependent pathway. While p53 does not seem to be involved in 5-FU induced apoptosis and cell cycle arrest in laryngeal carcinoma, further studies are needed to examine the roles of retinoblastoma protein and p21WAF1/CIP1 in laryngeal carcinoma receiving chemotherapy.
Authors:
Han Ching Liu; George G Chen; Alexander C Vlantis; Billy C S Leung; Michael C F Tong; C Andrew van Hasselt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer journal (Sudbury, Mass.)     Volume:  12     ISSN:  1528-9117     ISO Abbreviation:  Cancer J     Publication Date:    2006 Nov-Dec
Date Detail:
Created Date:  2007-01-08     Completed Date:  2007-10-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100931981     Medline TA:  Cancer J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  482-93     Citation Subset:  IM    
Affiliation:
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Antimetabolites, Antineoplastic / pharmacology*
Apoptosis / drug effects*
Carcinoma, Squamous Cell / drug therapy*
Cell Line, Tumor
DNA Replication / drug effects*
Fluorouracil / pharmacology*
G1 Phase / drug effects*
Humans
Laryngeal Neoplasms / drug therapy*
Signal Transduction / drug effects*
Tumor Suppressor Protein p53 / genetics
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Tumor Suppressor Protein p53; 51-21-8/Fluorouracil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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