Abstract
The biological activity of peroxisome proliferators (PPs) is mediated by a class of receptors, known as PPARs (PP-Activated Receptor), belonging to the nuclear receptor superfamily. Upon ligand binding, PPARs dimerize with retinoid receptors, translocate to the nucleus, recognize specific PP-responsive elements on DNA and transactivate a number of genes. Several processes are regulated by PPARs, such as mitochondrial and peroxisomal fatty acid uptake and β- oxidation, inflammation, intracellular lipid trafficking, cell proliferation and death. In addition, PPARs have been proposed to act as tumor suppressors or as tumor promoters, depending on the circumstances. In particular, PPs have been extensively studied for their hepatocarcinogenic action in rodents, most often ascribed to their antiapoptotic action. Recent evidence, however, has been provided about the antiproliferative, proapoptotic, and differentiation-promoting activities displayed by PPAR ligands. The present review will focus on the cytotoxic effects exerted by several PPs, among which clofibrate, on different types of tumor cells, with particular reference to the mechanisms of cell death and to their relevance to cancer induction and progression.
Keywords: Peroxisome proliferators, PPAR, clofibrate, apoptosis, cancer
Current Medicinal Chemistry
Title: Cytotoxic Properties of Clofibrate and other Peroxisome Proliferators: Relevance to Cancer Progression
Volume: 17 Issue: 4
Author(s): F. Penna, G. Bonelli, F. M. Baccino and P. Costelli
Affiliation:
Keywords: Peroxisome proliferators, PPAR, clofibrate, apoptosis, cancer
Abstract: The biological activity of peroxisome proliferators (PPs) is mediated by a class of receptors, known as PPARs (PP-Activated Receptor), belonging to the nuclear receptor superfamily. Upon ligand binding, PPARs dimerize with retinoid receptors, translocate to the nucleus, recognize specific PP-responsive elements on DNA and transactivate a number of genes. Several processes are regulated by PPARs, such as mitochondrial and peroxisomal fatty acid uptake and β- oxidation, inflammation, intracellular lipid trafficking, cell proliferation and death. In addition, PPARs have been proposed to act as tumor suppressors or as tumor promoters, depending on the circumstances. In particular, PPs have been extensively studied for their hepatocarcinogenic action in rodents, most often ascribed to their antiapoptotic action. Recent evidence, however, has been provided about the antiproliferative, proapoptotic, and differentiation-promoting activities displayed by PPAR ligands. The present review will focus on the cytotoxic effects exerted by several PPs, among which clofibrate, on different types of tumor cells, with particular reference to the mechanisms of cell death and to their relevance to cancer induction and progression.
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Cite this article as:
Penna F., Bonelli G., Baccino M. F. and Costelli P., Cytotoxic Properties of Clofibrate and other Peroxisome Proliferators: Relevance to Cancer Progression, Current Medicinal Chemistry 2010; 17 (4) . https://dx.doi.org/10.2174/092986710790192712
DOI https://dx.doi.org/10.2174/092986710790192712 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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