Activation of peroxisome proliferator-activated receptor (PPAR)-gamma by 15S-hydroxyeicosatrienoic acid parallels growth suppression of androgen-dependent prostatic adenocarcinoma cells

Pham, Hung; Banerjee, Tinku; Nalbandian, Gregory M.; Ziboh, Vincent A.

doi:10.1016/s0304-3835(02)00498-6

Cited by 25 publications

(12 citation statements)

References 22 publications

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“…First, PUFAs, including GLA, are known to serve as endogenous ligands of peroxisome proliferator activated receptors (PPARs) and to bind and activate all PPARs isoforms 31. Additionally, 15-HETE, one of the metabolites of GLA, has been reported to upregulate nuclear PPAR-γ expression 32. PPARs participate in regulating inflammatory responses by inhibiting monocyte expression of proinflammatory cytokines such as IL-6, IL-1β, and TNF-α 33.…”

Section: Discussionmentioning

confidence: 99%

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

et al. 2012

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PurposeThis study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions.Materials and MethodsSprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 µM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated.ResultsTwenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1.ConclusionGLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

et al. 2012

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“…The opposing effects of 15-LOX-1 and 15-LOX-2 metabolites are reliable to opposing effects on epidermal growth factor and insulin-like growth factor-1 signaling with, as a result, opposing effects on the regulation of a downstream target of MAPkinase signaling like PPARγ [118][119][120].…”

Section: -Lox and Cancermentioning

confidence: 99%

COX-2/5-LOX Dual Acting Anti-Inflammatory Drugs in Cancer Chemotherapy

Goossens¹,

Pommery²,

Henichart

2007

CTMC

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Emerging reports now indicate alterations of arachidonic acid metabolism with carcinogenesis and many COX and LOX inhibitors (used for the treatment of inflammatory diseases) are being investigated as potential anticancer drugs. Results from clinical trials seem to be encouraging but a better knowledge of the dynamic balance that shifts toward lipoxygenases (and different isoforms of LOXs) and cyclooxygenase-2 are essential to progress in the design of new drugs more specially directed on chemoprevention or chemotherapy of human cancers. So, on the basis of these results, it seemed useful to study the advantages of combination of COX inhibitor with LOX inhibitor and a next step will be the conception of dual inhibitors able to induce the anticarcinogenic and/or to inhibit the procarcinogenic enzymes responsible for polyunsaturated fatty acid metabolism. After a rapid summary of some recent reviews published on the involvement of different COX and LOX isoforms present in human cells, we will discuss on cross-talk reported between the downstream pathways which contribute to the development and progression of human cancers. This will lead us to evoke and to justify alternative strategies to develop agents that modulate multiple targets simultaneously with the aim of enhancing efficacy or improving safety relative to drugs that address only a single enzyme.

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“…15-Lox-2 (murine homologue 8-Lox) is downregulated in prostate cancer and esophageal cancers [157,158]. Its metabolite, 15-HETE, suppresses the formation of LTB4 and 5-HETE [159,160], inhibits Cox2 [161], and activates PPARγ [162,163]. 15-Lox-2 negatively regulates cell cycle in normal prostate epithelial cells [164].…”

Section: -Lox 12-lox and 15-lox Pathwaysmentioning

confidence: 99%

Five-Lipoxygenase Pathway of Arachidonic Acid Metabolism in Carcinogenesis and Cancer Chemoprevention

Chen¹,

Sood²,

Yang³

et al. 2006

CCDT

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Aberrant arachidonic acid metabolism has recently received intensive attention in the field of cancer research. Recent discoveries regarding the long-term cardiovascular side effects of cyclooxygenase 2 inhibitors have cast doubts on their use for cancer chemoprevention. Although such a problem does not undermine the importance of cyclooxygenase 2 as a cancer chemopreventive target, investigation into other AA-metabolizing pathways that are also important in inflammation and inflammation-associated carcinogenesis is necessary. Here, the important role of the 5-lipoxygenase pathway in carcinogenesis is reviewed. Inhibition of the 5-lipoxygenase pathways clearly has chemopreventive effects on various cancers, and hence further studies on its enzymes, metabolites and receptors for cancer chemoprevention and therapy are warranted.

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Activation of peroxisome proliferator-activated receptor (PPAR)-gamma by 15S-hydroxyeicosatrienoic acid parallels growth suppression of androgen-dependent prostatic adenocarcinoma cells

Cited by 25 publications

References 22 publications

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

COX-2/5-LOX Dual Acting Anti-Inflammatory Drugs in Cancer Chemotherapy

Five-Lipoxygenase Pathway of Arachidonic Acid Metabolism in Carcinogenesis and Cancer Chemoprevention

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