Peroxisome proliferator-activated receptors and inflammation

Moraes, Leonardo A.; Piqueras, Laura; Bishop‐Bailey, David

doi:10.1016/j.pharmthera.2005.08.007

Cited by 336 publications

(307 citation statements)

References 158 publications

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“…However, a number of studies have consistently suggested that PPAR-␦ induces angiogenesis, possibly by activating VEGFA expression (7,12,55). Therefore, understanding the molecular details of PPAR-␦ transactivation of VEGFA could shed light on possible roles of PPAR-␦ in tumor formation.…”

Section: Discussionmentioning

confidence: 99%

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

Hwang

Kim

Jeong

2012

Journal of Biological Chemistry

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Background: Mechanism of VEGFA transcription by complex interplay of ␤-catenin and PPAR-␦ remains elusive. Results: The VEGFA promoter was dynamically occupied by ␤-catenin, TCF-4, and PPAR-␦. ␤-Catenin also bound downstream region of the VEGFA gene. Conclusion: ␤-Catenin is responsible for the formation of chromatin loops, which is relieved by PPAR-␦ activation. Significance: Proposed mechanism could provide clues for VEGFA-mediated colon cancer cell initiation.

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Section: Discussionmentioning

confidence: 99%

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

Hwang

Kim

Jeong

2012

Journal of Biological Chemistry

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“…The antiinflammatory effect of PPAR␣ ligands is mediated notably through inhibition of inducible NOS, COX-2, and TNF␣ (31). Inflammatory cells present in the tumor play an important tumor-promoting role (26) by secretion of trophic cytokines for tumor cells as well as proangiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

PPARα agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition

Panigrahy

Kaipainen

Huang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

244

206

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Angiogenesis and inflammation are central processes through which the tumor microenvironment influences tumor growth. We have demonstrated recently that peroxisome proliferatoractivated receptor (PPAR)␣ deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of thrombospondin (TSP)-1 and prevents tumor growth. Hence, we speculated that pharmacologic activation of PPAR␣ would promote tumor growth. Surprisingly, the PPAR␣ agonist fenofibrate potently suppressed primary tumor growth in mice. This effect was not mediated by cancer-cell-autonomous antiproliferative mechanisms but by the inhibition of angiogenesis and inflammation in the host tissue. Although PPAR␣-deficient tumors were still susceptible to fenofibrate, absence of PPAR␣ in the host animal abrogated the potent antitumor effect of fenofibrate. In addition, fenofibrate suppressed endothelial cell proliferation and VEGF production, increased TSP-1 and endostatin, and inhibited corneal neovascularization. Thus, both genetic abrogation of PPAR␣ as well as its activation by ligands cause tumor suppression via overlapping antiangiogenic pathways. These findings reveal the potential utility of the well tolerated PPAR␣ agonists beyond their use as lipid-lowering drugs in anticancer therapy. Our results provide a mechanistic rationale for evaluating the clinical benefits of PPAR␣ agonists in cancer treatment, alone and in combination with other therapies. stroma ͉ inflammation ͉ fibrates ͉ microenvironment P eroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors comprising three isoforms, PPAR␣, PPAR␦, and PPAR␥, which act as ligand-activated transcriptional factors. PPARs play key roles in energy homeostasis by modulating glucose and lipid metabolism and transport (1). PPAR␣ is also critical in inflammation (2) and is the molecular target of the fibrate class of drugs, such as fenofibrate, which act as agonistic ligands of PPAR␣.Long-term administration of certain PPAR␣ agonists (clofibrate and WY14643) induces hepatocarcinogenesis in rodents but not in humans (3). Consequently, PPAR␣ has not been established as a molecular target for cancer therapy by its agonistic ligands. In contrast, PPAR␥ and PPAR␦ agonists have been extensively studied to evaluate their anticancer effects because of their antiproliferative, proapoptotic, antiapoptotic, and differentiation-promoting activity (4). However, recent studies have revealed the expression of PPAR␣ in tumor cells (5, 6), and PPAR␣ ligands suppress the growth of several cancer lines, including colon, breast, endometrial and skin, in vitro (7-10). PPAR␣ ligands also suppress the metastatic potential of melanoma cells in vitro and in vivo (11,12). Furthermore, PPAR␣ ligands decrease tumor development in murine colon carcinogenesis (7). Clofibric acid inhibits the growth of human ovarian cancer in mice (13). Most recently, the PPAR␣ agonist WY14643 suppresses tumorigenesis in a PPAR␣-dependent manner (14).Together, these data suggest that PPAR...

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“…Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily that function as ligand-inducible transcription factors and control the expression of multiple target genes [2,3]. Pharmacological activation of each of three PPAR isoforms (α, β/δ and γ) is effective at correcting a specific aspect of the metabolic syndrome, such as insulin resistance, dyslipidaemia and hyperglycaemia [2].…”

Section: Introductionmentioning

confidence: 99%

Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice

Luo

et al. 2016

Diabetologia

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Peroxisome proliferator-activated receptors and inflammation

Cited by 336 publications

References 158 publications

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

β-Catenin and Peroxisome Proliferator-activated Receptor-δ Coordinate Dynamic Chromatin Loops for the Transcription of Vascular Endothelial Growth Factor A Gene in Colon Cancer Cells

PPARα agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition

Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice

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