The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention

Published on Mar 1, 2012in Nature Reviews Cancer53.03
Ā· DOI :10.1038/NRC3214
Jeffrey M. Peters82
Estimated H-index: 82
(PSU: Pennsylvania State University),
Yatrik M. Shah46
Estimated H-index: 46
(UM: University of Michigan),
Frank J. Gonzalez190
Estimated H-index: 190
Sources
Abstract
Abstract Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. Although all of these functions might contribute to the influence of PPARs in carcinogenesis, there is a distinct need for a review of the literature and additional experimentation to determine the potential for targeting PPARs for cancer therapy and cancer chemoprevention. As PPAR agonists include drugs that are used for the treatment of metabolic diseases, a more complete understanding of the roles of PPARs in cancer will aid in determining any increased cancer risk for patients undergoing therapy with PPAR agonists.
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References231
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#1Dingzhi Wang (University of Texas MD Anderson Cancer Center)H-Index: 38
#2Wei Ning (VUMC: Vanderbilt University Medical Center)H-Index: 11
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Peroxisome proliferator-activated receptor Ī“ confers resistance to peroxisome proliferator-activated receptor Ī³-induced apoptosis in colorectal cancer cells
Source
#1Huijing Fu (WashU: Washington University in St. Louis)H-Index: 6
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Budesonide, a synthetic glucocorticoid used for treating asthma, and pioglitazone, a synthetic peroxisome proliferator-activated receptors Ī³ ligand used for the treatment of diabetes, were evaluated for their combinational chemopreventive efficacy on mouse lung cancer using female A/J mice with benzo(a)pyrene used as the carcinogen. All chemopreventive treatments began 2-wk post-carcinogen treatment and continued daily for 20ā€‰wk. Budesonide was administered by the aerosol route using an improved...
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#1Jeffrey M. Peters (PSU: Pennsylvania State University)H-Index: 82
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Critical physiological roles of peroxisome proliferator-activated receptor-Ī²/Ī“ (PPARĪ²/Ī“) include the regulation glucose and lipid homeostasis, cellular differentiation and modulation of inflammation. The potential for targeting PPARĪ²/Ī“ for the prevention and treatment of metabolic diseases or cancer, is compromised because of major inconsistencies in the literature. This is due primarily to uncertainty regarding the effect of PPARĪ²/Ī“ and its activation on cell proliferation, apoptosis and cell s...
Source
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Peroxisome proliferator-activated receptor-Ī²/Ī“ (PPARĪ²/Ī“) function and receptor cross-talk with other nuclear receptors, including PPARĪ³ and retinoic acid receptors (RARs), was examined using stable human HaCaT keratinocyte cell lines over-expressing PPARĪ²/Ī“ or PPARĪ³. Enhanced ligand-induced expression of two known PPAR target genes, adipocyte differentiation-related protein (ADRP) and angiopoietin-like protein 4 (ANGPTL4), was found in HaCaT keratinocytes over-expressing PPARĪ²/Ī“ or PPARĪ³. Over-e...
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Peroxisome proliferator-activated receptor Ī²/Ī“ (PPARĪ²/Ī“) is a ligand-regulated nuclear receptor with essential functions in metabolism and inflammation. We have synthesized a new derivative [methyl 3-(N-(4-(hexylamino)-2-methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (ST247) structurally related to the published PPARĪ²/Ī“ inhibitory ligand methyl 3-(N-(2-methoxy-4-(phenylamino)phenyl)sulfamoyl)thiophene-2-carboxylate (GSK0660). ST247 has a higher affinity to PPARĪ²/Ī“ than GSK0660, and at equimolar...
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Cells are constantly exposed to a large variety of lipids. Traditionally, these molecules were thought to serve as simple energy storing molecules. More recently it has been realized that they can also initiate and regulate signaling events that will decisively influence development, cellular differentiation, metabolism and related functions through the regulation of gene expression. Multicellular organisms dedicate a large family of nuclear receptors to these tasks. These proteins combine the d...
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Purpose We have recently reported that peroxisome proliferator-activated receptor gamma (PPARĪ³) ligands produce antitumor effects against human ovarian cancer in conjunction with reduction in angiogenesis and induction of apoptosis via regulating prostaglandin (PG) E2 level. In this study, we investigated the effects of combination of ciglitazone, a PPARĪ³ ligand, and cisplatin, a cytotoxic anti-cancer drug, on growth of ovarian cancer.
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