Mice lacking epidermal PPARγ exhibit a marked augmentation in photocarcinogenesis associated with increased UVB‐induced apoptosis, inflammation and barrier dysfunction

Chang

BioMed Research International

et al. 2014

The purpose of this study was to investigate if PPARγ plays a role in the melanogenesis. B16/F10 cells were divided into five groups: control, melanin stimulating hormone (α-MSH), α-MSH+retinol, α-MSH+GW9662 (PPARγ antagonist), and GW9662. Cells in the control group were cultured in the Dulbecco's modified Eagle's medium (DMEM) for 48 hrs. To initiate the melanogenesis, cells in all α-MSH groups were cultured in medium containing α-MSH (10 nM) for 48 hrs. Cells were treated simultaneously with retinol (5 μM) in the α-MSH+retinol group. Instead of retinol, GW9662 (10 μM) was cocultured in the α-MSH+GW9662 group. Cells in the final group were cultured in the DMEM with GW9662. All the analyses were carried out 48 hours after treatments. The α-MSH was able to increase cell number, melanin production, and the activity of tyrosinase, the limiting enzyme in melanogenesis. These α-MSH-induced changes were prevented either by retinol or by GW9662. Further analyses of the activities of antioxidant enzymes including glutathione, catalase, and the superoxide dismutase (SOD) showed that α-MSH treatment raised the activity of SOD which was dependent on PPARγ level. According to our results, the α-MSH-induced melanogenesis was PPARγ dependent, which also modulated the expression of SOD.

Section: Discussionsupporting

confidence: 58%

Inhibition of Peroxisome Proliferator-Activated Receptor Gamma Prevents the Melanogenesis in Murine B16/F10 Melanoma Cells

Chang

BioMed Research International

et al. 2014

“…Studies by us and others have shown that this treatment consistently results in initial tumor formation within 11–12 weeks of treatment (19, 20). We therefore discontinued UVB treatments after 10 weeks of treatment.…”

Section: Methodsmentioning

confidence: 87%

“…Examining Hgb content beginning two weeks after cessation of UVB dosing allowed us to examine changes in blood supply at the time when tumors initially begin to appear in this mouse model (19, 20), but after the acute sunburn effect had resolved. This also mimics human behavior, in which sun-avoidance strategies are often employed only after significant cutaneous photodamage is apparent or a first tumor is found.…”

Section: Resultsmentioning

confidence: 99%

“…SKH-1 hairless albino mice (Charles River Laboratories, Wilmington, MA, USA) were irradiated with one minimal erythema dose of UVB (2240 J/m 2 ) three times per week (M,W,F) as previously described (19). Studies by us and others have shown that this treatment consistently results in initial tumor formation within 11–12 weeks of treatment (19, 20).…”

Section: Methodsmentioning

confidence: 99%

“…Paraffin-embedded sections were stained with hematoxylin & eosin (H&E) and examined by dermatopathologists for the presence of small tumors not visible macroscopically. Tumors were classified as previously described ((19) and Supplemental Methods). …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Spatiotemporal Assessments of Dermal Hyperemia Enable Accurate Prediction of Experimental Cutaneous Carcinogenesis as well as Chemopreventive Activity

Konger

Sahu

et al. 2013

Cancer Research

Self Cite

Field cancerization refers to areas of grossly normal epithelium that exhibit increased risk for tumor occurrence. Unfortunately, elucidation of the locoregional changes that contribute to increased tumor risk is difficult due to the inability to visualize the field. In this study, we use a non-invasive optical-based imaging approach to detail spatiotemporal changes in subclinical hyperemia that occur during experimental cutaneous carcinogenesis. After acute inflammation from 10 weeks of ultraviolet B (UVB) irradiation subsides, small areas of focal hyperemia form and were seen to persist and expand long after cessation of UVB irradiation. We show that these persistent early hyperemic foci reliably predict sites of angiogenesis and overlying tumor formation. Over 96% of tumors (57 of 59) that developed following UVB or DMBA/PMA treatment developed in sites of preexisting hyperemic foci. Hyperemic foci were multifocal and heterogeneously distributed and represented a minor fraction of the carcinogen-treated skin surface (10.3% of the imaging area in vehicle treated animals). Finally, we also assessed the ability of the anti-inflammatory agent celecoxib to suppress hyperemia formation during photocarcinogenesis. The chemopreventive activity of celecoxib was shown to correlate with its ability to reduce the area of skin that exhibit these hyperemic foci, reducing the area of imaged skin containing hyperemic foci by 49.1%. Thus, we propose that a hyperemic switch can be exploited to visualize the cancerization field very early in the course of cutaneous carcinogenesis and provides insight into the chemopreventive activity of the anti-inflammatory agent celecoxib.

Molecular Carcinogenesis

Evidence that peroxisome proliferator‐activated receptor γ suppresses squamous carcinogenesis through anti‐inflammatory signaling and regulation of the immune response

Ren

Konger

2019

Self Cite

A variety of evidence suggests that peroxisome proliferator‐activated receptor (PPAR)γ agonists may represent a potential pharmacologic target in the prevention or treatment of skin cancer. In particular, recent reports suggest that PPARγ activation may exert at least some of its anti‐neoplastic effects through the suppression of tumor promoting chronic inflammation as well as by strengthening antitumor immune responses. This activity is thought to occur through a distinct mode of ligand interaction with PPARγ that causes transrepression of transcription factors that are involved in inflammatory and immunomodulatory signaling. However, current thiazolidinedione (TZD)‐type PPARγ agonists have significant safety concerns that limit their usefulness as a preventive or therapeutic option. Due to the relatively large ligand binding pocket of PPARγ, a diverse group of ligands can be seen to interact with distinct modes of binding to PPARγ, leading to the phenomenon of partial agonist activity and selective PPARγ modulators (SPPARγM). This has led to the development of ligands that are tailored to deliver desired pharmacologic activity, but lack some of the negative side effects associated with full agonists, such as the currently utilized TZD‐type PPARγ agonists. In addition, there is evidence that a number of phytochemicals that are currently being touted as antineoplastic nutraceuticals also possess PPARγ activity that may partially explain their pharmacologic activity. We propose that one or more of these partial agonists, SPPARγMs, or putative phytochemical PPARγ ligands could presumably be used as a starting point to design more efficacious anti‐neoplastic PPARγ ligands that lack adverse pharmacological effects.