Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta).
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Kim DJ, Prabhu KS, Gonzalez FJ, Peters JM
Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta).
Carcinogenesis. 2006 May;27(5):1105-12. Epub 2006 Jan 16.
- PubMed ID
- 16418176 [ View in PubMed]
- Abstract
Inhibition of cyclooxygenase-2 (COX2) by non-steroidal anti-inflammatory drugs (NSAID) is known to suppress skin carcinogenesis. It was further suggested that inhibition of COX2-derived prostaglandins by NSAIDs could reduce levels of putative endogenous ligands of peroxisome proliferator-activated receptor-beta (PPARbeta), and these ligands could potentiate tumorigenesis. However, it is currently unclear whether ligand activation of PPARbeta either inhibits or potentiates carcinogenesis. The present studies were designed to examine the mechanism of NSAID-mediated chemoprevention in skin, and, in particular, to determine the role of PPARbeta in this process. A two-stage skin carcinogenicity bioassay was performed using wild-type and PPARbeta-null mice that were fed either a control diet or one containing 0.32 g sulindac/kg diet. Significant inhibition of chemically induced skin carcinogenesis was observed in both wild-type and PPARbeta-null mice, and this was associated with a marked decrease in the concentration of skin prostaglandins including PGE(2) and PGI(2). Results from these studies demonstrate that inhibition of COX2 by dietary sulindac in mouse skin can effectively inhibit chemically induced skin carcinogenesis, and suggest that the mechanism underlying this chemopreventive effect is independent of PPARbeta. Additionally, results from these studies do not support the hypothesis that ligand activation of PPARbeta by COX-derived metabolites potentiates chemically induced skin carcinogenesis.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Sulindac Peroxisome proliferator-activated receptor delta Protein Humans UnknownNegative modulatorDetails