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

Details

Serval ID
serval:BIB_F8D4CE10B0F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer.
Journal
Gut
Author(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
Publication state
Published
Issued date
2003
Volume
52
Number
9
Pages
1317-1322
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
24/01/2008 15:44
Last modification date
20/08/2019 16:24
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