These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: 5-fluorouracil mediates apoptosis and G1/S arrest in laryngeal squamous cell carcinoma via a p53-independent pathway.
    Author: Liu HC, Chen GG, Vlantis AC, Leung BC, Tong MC, van Hasselt CA.
    Journal: Cancer J; 2006; 12(6):482-93. PubMed ID: 17207318.
    Abstract:
    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.
    [Abstract] [Full Text] [Related] [New Search]