Peroxisome Proliferator-Activated Receptor Gamma (PPARγ as a Novel Target for Prostate Cancer

Smith, Matthew R.; Kantoff, Philip W.

doi:10.1023/a:1015670126203

Cited by 25 publications

(4 citation statements)

References 23 publications

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“…Then, PPARg/RXRa heterodimers can be activated by the ligation of PPARg or RXRa ligands, but the combination of retinoids with PPARg ligands and simultaneous ligation of both PPARg and RXRa may be beneficial and may maximize their activation (Nolte et al, 1998;Desvergne and Wahli, 1999). PPARg can be found in tumour tissues including human breast cancer (Mueller et al, 1998), lung cancer (Chang and Szabo, 2000;Roman, 2008), colon cancer (Sarraf et al, 1998;Kitamura et al, 1999), prostate cancer (Hisatake et al, 2000;Smith and Kantoff, 2002), pancreatic cancer (Motomura et al, 2000), as well as in human leukaemia and lymphoma cells (Asou et al, 1999;Padilla et al, 2002;Laurora et al, 2003). Activation of PPARg by its ligands has potential anti-neoplastic effects in these malignancies (Koeffler, 2003).…”

Section: Retinoids Act As Tumour-suppressive Agentsmentioning

confidence: 99%

Retinoids: novel immunomodulators and tumour‐suppressive agents?

Carratù

Marasco

Mangialardi

et al. 2012

British J Pharmacology

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Retinoids play important roles in the transcriptional activity of normal, degenerative and tumour cells. Retinoid analogues may be promising therapeutic agents for the treatment of immune disorders as different as type I diabetes and systemic lupus erythematosus. In addition, the use of retinoids in cancer treatment has progressed significantly in the last two decades; thus, numerous retinoid compounds have been synthesized and tested. In this paper, the actual or potential use of retinoids as immunomodulators or tumour‐suppressive agents is discussed.

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Section: Retinoids Act As Tumour-suppressive Agentsmentioning

confidence: 99%

Retinoids: novel immunomodulators and tumour‐suppressive agents?

Carratù

Marasco

Mangialardi

et al. 2012

British J Pharmacology

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“…Ligands for PPARγ include the eicosanoids 15S–Hydroxyeicosatetraenoic acid (15-HETE) (Bhatia et al, 2003, Shappell et al, 2001b) and the prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) (Matsuyama et al, 2005, Soares et al, 2005), docosahexaenoic acid (DHA) (Yu et al, 2008), polyunsaturated fatty acid (PUFA) (Calder, 2008), and nonsteroidal anti-inflammatory drugs (NSAID) (Romeiro et al, 2008) as well as synthetic Thiazolidinedione (TZD) drugs (Rosen and Spiegelman, 2001). The TZDs rosiglitazone and pioglitazone are currently used in the clinic to treat patients with type II diabetes, due to their ability to increase insulin sensitivity by stimulating glucose uptake (Smith and Kantoff, 2002). However, use of these drugs has been severely curtailed of late because of cardiovascular side effects and also because clinical trials are showing little improvement over more established therapies for diabetes treatments (Lindberg and Astrup, 2007).…”

Section: Peroxisome Proliferator-activated Receptor Gamma (Pparγ) mentioning

confidence: 99%

PPARγ: A molecular link between systemic metabolic disease and benign prostate hyperplasia

et al. 2011

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The emergent epidemic of metabolic syndrome and its complex list of sequelae mandate a more thorough understanding of benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) in the context of systemic metabolic disease. Here we discuss the nature and origins of BPH, examine its role as a component of LUTS and review retrospective clinical studies that have drawn associations between BPH/LUTS and type II diabetes, inflammation and dyslipidemia. PPARγ signaling, which sits at the nexus of systemic metabolic disease and BPH/LUTS through its regulation of inflammation and insulin resistance is proposed as a candidate for molecular manipulation in regard to BPH/LUTS. Finally, we introduce new cell and animal models that are being used to study the consequences of obesity, diabetes and inflammation on benign prostatic growth.

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“…Tissue-based and in vitro studies suggest that alterations in PPARγ activity may be involved in Pca and that PPARγ may be a candidate target for Pca therapy (12-14). …”

Section: Introductionmentioning

confidence: 99%

Disruption of PPARγ signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy

et al. 2009

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Peroxisome proliferator-activated receptor-gamma (PPARγ) regulates the interface between cellular lipid metabolism, redox status and organelle differentiation. Conditional prostatic epithelial knockout of PPARγ in mice resulted in focal hyperplasia which developed into mouse prostatic intraepithelial neoplasia (mPIN). The grade of PIN became more severe with time. Electron microscopy (EM) showed accumulated secondary lysosomes containing cellular organelles and debris suggestive of autophagy. Consistent with this analysis the autophagy marker LC3 was found to be upregulated in areas of PIN in PPARγ KO tissues. We selectively knocked down PPARγ2 isoform in wild-type mouse prostatic epithelial cells and examined the consequences of this in a tissue recombination model. Histopathologically grafted tissues resembled the conditional PPARγ KO mouse prostates. EM studies of PPARγ- and PPARγ2-deficient epithelial cells in vitro were suggestive of autophagy, consistent with the prostatic tissue analysis. This was confirmed by examining expression of beclin-1 and LC3. Gene expression profiling in PPARγ-/γ2-deficient cells indicated a major dysregulation of cell cycle control and metabolic signaling networks related to peroxisomal and lysosomal maturation, lipid oxidation and degradation. The putative autophagic phenotypes of PPARγ-deficient cells could be rescued by re-expression of either γ1 or γ2 isoform. We conclude that disruption of PPARγ signaling results in autophagy and oxidative stress during mPIN pathogenesis.

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Peroxisome Proliferator-Activated Receptor Gamma (PPARγ as a Novel Target for Prostate Cancer

Cited by 25 publications

References 23 publications

Retinoids: novel immunomodulators and tumour‐suppressive agents?

Retinoids: novel immunomodulators and tumour‐suppressive agents?

PPARγ: A molecular link between systemic metabolic disease and benign prostate hyperplasia

Disruption of PPARγ signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy

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