Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer.

Détails

ID Serval
serval:BIB_F8D4CE10B0F3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer.
Périodique
Gut
Auteur(s)
Jackson L., Wahli W., Michalik L., Watson S.A., Morris T., Anderton K., Bell D.R., Smith J.A., Hawkey C.J., Bennett A.J.
ISSN
0017-5749 (Print)
ISSN-L
0017-5749
Statut éditorial
Publié
Date de publication
2003
Volume
52
Numéro
9
Pages
1317-1322
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors involved in genetic control of many cellular processes. PPAR and PPAR have been implicated in colonic malignancy. Here we provide three lines of evidence suggesting an inhibitory role for PPAR in colorectal cancer development.
METHODS: Levels of PPAR mRNA and protein in human colorectal cancers were compared with matched non-malignant mucosa using RNAse protection and western blotting. APC(Min)/+ mice were randomised to receive the PPAR activator methylclofenapate 25 mg/kg or vehicle for up to 16 weeks, and small and large intestinal polyps were quantified by image analysis. The effect of methylclofenapate on serum stimulated mitogenesis (thymidine incorporation), linear cell growth, and annexin V and propidium iodide staining were assessed in human colonic epithelial cells.
RESULTS: PPAR (mRNA and protein) expression levels were significantly depressed in colorectal cancer compared with matched non-malignant tissue. Methylclofenapate reduced polyp area in the small intestine from 18.7 mm(2) (median (interquartile range 11.1, 26.8)) to 9.90 (4.88, 13.21) mm(2) (p=0.003) and in the colon from 9.15 (6.31, 10.5) mm(2) to 3.71 (2.71, 5.99) mm(2) (p=0.009). Methylclofenapate significantly reduced thymidine incorporation and linear cell growth with no effect on annexin V or propidium iodide staining.
CONCLUSIONS: PPAR may inhibit colorectal tumour progression, possibly via inhibition of proliferation, and may be an important therapeutic target.
Mots-clé
Animals, Anticarcinogenic Agents/pharmacology, Clofenapate/pharmacology, Colorectal Neoplasms/genetics, Colorectal Neoplasms/prevention & control, Female, Gene Expression Regulation, Neoplastic, Humans, Intestinal Polyps/genetics, Intestinal Polyps/prevention & control, Ligands, Male, Mice, Mice, Inbred C57BL, RNA, Messenger/genetics, Random Allocation, Receptors, Cytoplasmic and Nuclear/drug effects, Receptors, Cytoplasmic and Nuclear/genetics, Transcription Factors/drug effects, Transcription Factors/genetics, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:44
Dernière modification de la notice
20/08/2019 16:24
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