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Mitochondria, PPARs, and Cancer: Is Receptor-Independent Action of PPAR Agonists a Key?
Joint Authors
Giardina, Bruno
Scatena, Roberto
Bottoni, Patrizia
Source
Issue
Vol. 2008, Issue 2008 (31 Dec. 2008), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2008-06-26
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Before the discovery of peroxisome proliferator activated receptors (PPARs), it was well known that certain drugs considered as classical PPAR-alpha agonists induced hepatocarcinoma or peroxisome proliferation in rodents.
These drugs were derivatives of fibric acid, and they included clofibrate, bezafibrate, and fenofibrate.
However, such toxicity has never been observed in human patients treated with these hypolipidemic drugs.
Thiazolidinediones are a new class of PPAR activators showing greater specificity for the γ isoform of PPARs.
These drugs are used as insulin sensitizers in the treatment of type II diabetes.
In addition, they have been shown to induce cell differentiation or apoptosis in various experimental models of cancer.
PPAR-α ligands have also been shown to induce cancer cell differentiation and, paradoxically, PPAR-γ drug activators have been reported to act as carcinogens.
The confusing picture that emerges from these data is further complicated by the series of intriguing side effects observed following administration of pharmacological PPAR ligands (rhabdomyolysis, liver and heart toxicity, anemia, leucopenia).
These side effects cannot be easily explained by simple interactions between the drug and nuclear receptors.
Rather, these side effects seem to indicate that the ligands have biological activity independent of the nuclear receptors.
Considering the emerging role of mitochondria in cancer and the potential metabolic connections between this organelle and PPAR physiology, characterization of the reciprocal influences is fundamental not only for a better understanding of cancer biology, but also for more defined pharmacotoxicological profiles of drugs that modulate PPARs.
American Psychological Association (APA)
Scatena, Roberto& Bottoni, Patrizia& Giardina, Bruno. 2008. Mitochondria, PPARs, and Cancer: Is Receptor-Independent Action of PPAR Agonists a Key?. PPAR Research،Vol. 2008, no. 2008, pp.1-10.
https://search.emarefa.net/detail/BIM-988183
Modern Language Association (MLA)
Scatena, Roberto…[et al.]. Mitochondria, PPARs, and Cancer: Is Receptor-Independent Action of PPAR Agonists a Key?. PPAR Research No. 2008 (2008), pp.1-10.
https://search.emarefa.net/detail/BIM-988183
American Medical Association (AMA)
Scatena, Roberto& Bottoni, Patrizia& Giardina, Bruno. Mitochondria, PPARs, and Cancer: Is Receptor-Independent Action of PPAR Agonists a Key?. PPAR Research. 2008. Vol. 2008, no. 2008, pp.1-10.
https://search.emarefa.net/detail/BIM-988183
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-988183