Agonists of Peroxisome Proliferator-Activated Receptor γ Inhibit Cell Growth in Malignant Melanoma

Mößner, Rotraut; Schulz, Ulrike; Krüger, Ullrich; Neumann, Christine; Reich, Kristian; Middel, Peter; Schinner, Sven; Füzesi, L.

doi:10.1046/j.1523-1747.2002.01861.x

Cited by 69 publications

(77 citation statements)

References 28 publications

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“…In addition to nonmelanoma skin cancer, there have been reports of a possible role of PPARs in malignant melanoma (i.e., PPARg activation was reported to inhibit the proliferation of human melanoma and melanocyte cell lines) (38,109). A recent report, however, evaluating the putative risk of genetic polymorphisms in the PPARg gene for the development of malignant mela- noma has yielded inconsistent results in two independent case-control studies (110).…”

Section: Role Of Ppar In Skin Cancermentioning

confidence: 99%

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

Schmuth

Jiang

Dubrac

et al. 2008

Journal of Lipid Research

183

160

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The epidermis is a very active site of lipid metabolism, and all peroxisome proliferator-activated receptor (PPAR) and liver X receptor (LXR) isoforms are expressed in the epidermis. Activation of PPARa, -b/d, or -g or LXRs stimulates keratinocyte differentiation. Additionally, activation of these receptors also improves permeability barrier homeostasis by a number of mechanisms, including stimulating epidermal lipid synthesis, increasing lamellar body formation and secretion, and increasing the activity of enzymes required for the extracellular processing of lipids in the stratum corneum, leading to the formation of lamellar membranes that mediate permeability barrier function. The stimulation of keratinocyte differentiation and permeability barrier formation also occurs during fetal development, resulting in accelerated epidermal development. PPAR and LXR activation regulates keratinocyte proliferation and apoptosis, and studies have shown that these receptors play a role in cutaneous carcinogenesis. Lastly, PPAR and LXR activation is anti-inflammatory, reducing inflammation in animal models of allergic and irritant contact dermatitis. Because of their broad profile of beneficial effects on skin homeostasis, PPAR and LXR have great potential to serve as drug targets for common skin diseases such as psoriasis, atopic dermatitis, and skin

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Section: Role Of Ppar In Skin Cancermentioning

confidence: 99%

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

Schmuth

Jiang

Dubrac

et al. 2008

Journal of Lipid Research

183

160

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“…The antitumorigenic effects of PPARg ligands have been well documented (Yang and Frucht, 2001;Haydon et al, 2002;Mossner et al, 2002;Osawa et al, 2003). Numerous studies have demonstrated that troglitazone (TRO), a synthetic PPARg ligand, causes growth inhibition, induces differentiation, and triggers apoptosis of various human malignant cells (Asou et al, 1999;Clay et al, 1999;Demetri et al, 1999;Sugimura et al, 1999;Hisatake et al, 2000;Rumi et al, 2001;Takashima et al, 2001;Begum et al, 2002;Yoshizawa et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells

et al. 2004

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We previously reported that the PPARc agonist troglitazone (TRO) inhibits proliferation and induces apoptosis in human MCF-7 breast carcinoma cells. To understand the mechanisms of antiproliferative and pro-apoptotic effects of TRO, we screened a limited DNA array containing 23 genes involved in regulating either the cell cycle and/or apoptosis. Four of the 23 genes screened exhibited regulation by TRO, with growth arrest and DNA damage-inducible gene 45 (GADD45) being the most strongly upregulated. TRO induced GADD45 mRNA expression in a time-and dose-dependent manner. Depletion of GADD45 by siRNA abrogated TROinduced apoptosis in MCF-7 cells demonstrating the physiological relevance of GADD45 upregulation. Signaling pathways mediating TRO-induced GADD45 were also investigated. Several mitogen-activated protein kinase (MAPK) pathways were involved in the induction of GADD45 by TRO. Inhibition of the c-jun N-terminal kinase MAPK pathway by SP600125 partially abolished TRO-induced GADD45 mRNA, and protein expression and apoptosis. In contrast, inhibition of the p38 MAPK pathway by SB203580, or through overexpression of a dominant-negative mutant of p38 MAPK, augmented GADD45 mRNA induction and GADD45 promoter activation as well as cell apoptosis by TRO. Blockade of the extracellular signal-regulated kinase MAPK pathway by PD98059 also enhanced TRO's effects on GADD45 and apoptosis. Two other PPARc agonists pioglitazone and rosiglitazone did not induce GADD45 expression. Our finding of GADD45 induction by TRO may provide a new insight concerning the mechanisms for TRO's antiproliferative and pro-apoptotic effects in breast cancer cells.

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“…In melanoma cells, these antiproliferative effects of PPAR-c agonists were also reported [14,15,17]. The PPAR-c specific ligands 15-d-PGJ2, troglitazone, and rosiglitazone dose-dependently inhibited proliferation of melanoma cells at concentrations between 0 and 50 lM [14].…”

Section: Ppar-c Activators Inhibit Cell Growth In Human Melanocytesmentioning

confidence: 81%

“…The PPAR-c specific ligands 15-d-PGJ2, troglitazone, and rosiglitazone dose-dependently inhibited proliferation of melanoma cells at concentrations between 0 and 50 lM [14]. Ciglitazone and PGJ2 not only inhibited A375 and WM35 melanoma cell proliferation but also induced apoptosis [17].…”

Section: Ppar-c Activators Inhibit Cell Growth In Human Melanocytesmentioning

confidence: 98%

Peroxisome proliferator-activated receptors-γ activator, ciglitazone, inhibits human melanocyte growth through induction of apoptosis

Kang

Lee

et al. 2006

Arch Dermatol Res

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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. All three PPAR subtypes, PPAR-a, PPARb/d and PPAR-c are expressed in human melanocytes. In this study, we investigated the effects of PPAR-c activator on melanocyte growth, and apoptosis. The PPAR-c activators ciglitazone, troglitazone, and 15-deoxy-prostaglandin J2 inhibited melanocyte growth in a dose-dependent manner. This inhibitory effect of ciglitazone seemed to occur through induction of apoptosis. Apoptosis was increased after ciglitazone treatment, which was observed by the TUNEL method and flow cytometry. We noted a decrease in extracellular signal regulated kinase protein expression under ciglitazone treatment. Western blot analysis revealed an apparent time-dependent reduction in Bcl-2 protein levels in ciglitazone-treated melanocytes. In terms of Bax expression, a difference was not found. The expression of caspase-3 proteins was increased time-dependently with ciglitazone treatment. These results indicate that melanocyte growth and apoptosis may be modulated through PPAR-c and that ciglitazone, a PPAR-c activator, inhibits growth of human melanocytes by inducing apoptosis.

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Agonists of Peroxisome Proliferator-Activated Receptor γ Inhibit Cell Growth in Malignant Melanoma

Cited by 69 publications

References 28 publications

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells

Peroxisome proliferator-activated receptors-γ activator, ciglitazone, inhibits human melanocyte growth through induction of apoptosis

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