Document Detail

Effect of ligand troglitazone on peroxisome proliferator-activated receptor gamma expression and cellular growth in human colon cancer cells.
MedLine Citation:
PMID:  17143939     Owner:  NLM     Status:  MEDLINE    
AIM: To investigate the effect of troglitazone on pe-roxisome proliferator-activated receptor gamma (PPARgamma) expression and cellular growth in human colon cancer HCT-116 and HCT-15 cells and to explore the related molecular mechanism.
METHODS: Human colon cancer HCT-116 and HCT-15 cells cultured in vitro were treated with troglitazone. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to detect the effect of troglitazone on PPARgamma expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by flow cytometry. Apoptosis-related genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively.
RESULTS: The expression of PPARgamma in colon cancer HCT-116 and HCT-15 cells was up-regulated by troglitazone. Troglitazone inhibited proliferation, induced apoptosis and cell cycle G1 arrest in colon cancer cells. Troglitazone induced p53 expression in HCT-116 cells, but not in HCT-15 cells. The down-regulation of survivin and bcl-2 was found in both cell lines and up-regulation of bax was found only in HCT-116 cells, being consistent with growth inhibition in HCT-116 cells but not in HCT-15 cells. Troglitazone increased expression of p21(WAF1/CIP1) (p21), p27(KIP1) (p27) and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells.
CONCLUSION: Troglitazone is an inductor of PPARgamma in colon cancer cells and inhibits PPARgamma-dependently proliferation, which may attribute to cell cycle G1 arrest and apoptosis in colon cancer cells. Troglitazone may induce p53-independent apoptosis and p53-dependent expression of p21 and p27. Depending on cell background, different activation pathways may exist in colon cancer cells.
Mei Ming; Jie-Ping Yu; Xiang-Zhi Meng; Yan-Hong Zhou; Hong-Gang Yu; He-Sheng Luo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  12     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-04     Completed Date:  2009-06-11     Revised Date:  2014-09-07    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  7263-70     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / therapeutic use*
Apoptosis / genetics
Cell Cycle / genetics
Cell Division / drug effects
Cell Line, Tumor
Chromans / therapeutic use*
Colonic Neoplasms / genetics,  pathology*
Flow Cytometry
PPAR gamma / drug effects,  genetics*
Reverse Transcriptase Polymerase Chain Reaction
Thiazolidinediones / therapeutic use*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Chromans; 0/PPAR gamma; 0/Thiazolidinediones; 97322-87-7/troglitazone

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

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