Document Detail

Proteomic analysis of antiproliferative effects by treatment of 5-fluorouracil in cervical cancer cells.
MedLine Citation:
PMID:  15585135     Owner:  NLM     Status:  MEDLINE    
The global effects of 5-fluorouracil (FU) on cervical carcinoma cells were analyzed using an efficient proteomic method. More than 50 proteins showed a significant change in 5-FU-treated cervical carcinoma cells compared to control cells. Among them, 34 proteins have been identified by employing two-dimensional gel electrophoresis and MALDI-TOF-MS using peptide mass fingerprinting. In results, 22 proteins were upregulated (CIDE-B [cell death-inducing DFFA-like effector B], caspase-3, caspase-8, Apo-1/CD95 (Fas), etc.) and 12 proteins were downregulated (mitotic checkpoint protein BUB3, myc proto-oncogene protein [c-myc], src substrate cortactin, transforming protein p21A, etc.) by 5-FU treatment in HeLa cervical carcinoma cells as determined by spot volume (P <0.05). Our experiments showed that 5-FU engaged the mitochondrial apoptotic pathway involving cytosolic cytochrome c release and subsequent activation of caspase-9 and caspase-3 as well as the membrane death receptor (DR)-mediated apoptotic pathway involving activation of caspase-8 with an Apo-1/CD95 (Fas)-dependent fashion. In addition, we could observe reduction of HPV-18 E6/E7 gene expression and activation of p53, pRb, and p21waf1 proteins by 5-FU treatment in HeLa cervical carcinoma cells. In conclusion, we suggest that 5-FU suppresses the growth of cervical cancer cells not only by antiproliferative effect but also antiviral regulation. Our findings may offer new insights into the mechanism of anticancer effect affected by 5-FU treatment in cervical cancer cells and its mode of action.
Eun-Kyoung Yim; Keun-Ho Lee; Jun Sang Bae; Sung-Eun Namkoong; Soo-Jong Um; Jong-Sup Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  DNA and cell biology     Volume:  23     ISSN:  1044-5498     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-12-08     Completed Date:  2005-02-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  769-76     Citation Subset:  IM    
Department of Medical Bioscience, Graduate School of Catholic University, Seoul, Republic of Korea.
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MeSH Terms
Antimetabolites, Antineoplastic / pharmacology*
Base Sequence
Cell Division / drug effects*
DNA Primers
Electrophoresis, Gel, Two-Dimensional
Fluorouracil / pharmacology*
Hela Cells
Reverse Transcriptase Polymerase Chain Reaction
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Uterine Cervical Neoplasms / pathology*
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/DNA Primers; 0/Proteome; 51-21-8/Fluorouracil

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