Dataset Information

Are FDA-Approved Sunscreen Components Effective in Preventing Solar UV-Induced Skin Cancer?

ABSTRACT: Solar ultraviolet (SUV) exposure is a major risk factor in the etiology of cutaneous squamous cell carcinoma (cSCC). People commonly use sunscreens to prevent SUV-induced skin damage and cancer. Nonetheless, the prevalence of cSCC continues to increase every year, suggesting that commercially available sunscreens might not be used appropriately or are not completely effective. In the current study, a solar simulated light (SSL)-induced cSCC mouse model was used to investigate the efficacy of eight commonly used FDA-approved sunscreen components against skin carcinogenesis. First, we tested FDA-approved sunscreen components for their ability to block UVA or UVB irradiation by using VITRO-SKIN (a model that mimics human skin properties), and then the efficacy of FDA-approved sunscreen components was investigated in an SSL-induced cSCC mouse model. Our results identified which FDA-approved sunscreen components or combinations are effective in preventing cSCC development. Not surprisingly, the results indicated that sunscreen combinations that block both UVA and UVB significantly suppressed the formation of cutaneous papillomas and cSCC development and decreased the activation of oncoproteins and the expression of COX-2, keratin 17, and EGFR in SSL-exposed SKH-1 (Crl:SKH1-Hrhr) hairless mouse skin. Notably, several sunscreen components that were individually purported to block both UVA and UVB were ineffective alone. At least one component had toxic effects that led to a high mortality rate in mice exposed to SSL. Our findings provide new insights into the development of the best sunscreen to prevent chronic SUV-induced cSCC development.

SUBMITTER: Bode AM

PROVIDER: S-EPMC7407267 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Are FDA-Approved Sunscreen Components Effective in Preventing Solar UV-Induced Skin Cancer?

Bode Ann M AM Roh Eunmiri E

Cells 20200711 7

Solar ultraviolet (SUV) exposure is a major risk factor in the etiology of cutaneous squamous cell carcinoma (cSCC). People commonly use sunscreens to prevent SUV-induced skin damage and cancer. Nonetheless, the prevalence of cSCC continues to increase every year, suggesting that commercially available sunscreens might not be used appropriately or are not completely effective. In the current study, a solar simulated light (SSL)-induced cSCC mouse model was used to investigate the efficacy of eig ...[more]

PMID: 32664608

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Project description:An urgent need exists for the development of more efficacious molecular strategies targeting nonmelanoma skin cancer (NMSC), the most common malignancy worldwide. Inflammatory signaling downstream of Toll-like receptor 4 (TLR4) has been implicated in several forms of tumorigenesis, yet its role in solar UV-induced skin carcinogenesis remains undefined. We have previously shown in keratinocyte cell culture and SKH-1 mouse epidermis that topical application of the specific TLR4 antagonist resatorvid (TAK-242) blocks acute UV-induced AP-1 and NF-?B signaling, associated with downregulation of inflammatory mediators and MAP kinase phosphorylation. We therefore explored TLR4 as a novel target for chemoprevention of UV-induced NMSC. We selected the clinical TLR4 antagonist resatorvid based upon target specificity, potency, and physicochemical properties. Here, we confirm using ex vivo permeability assays that topical resatorvid can be effectively delivered to skin, and using in vivo studies that topical resatorvid can block UV-induced AP-1 activation in mouse epidermis. We also report that in a UV-induced skin tumorigenesis model, topical resatorvid displays potent photochemopreventive activity, significantly suppressing tumor area and multiplicity. Tumors harvested from resatorvid-treated mice display reduced activity of UV-associated signaling pathways and a corresponding increase in apoptosis compared with tumors from control animals. Further mechanistic insight on resatorvid-based photochemoprevention was obtained from unsupervised hierarchical clustering analysis of protein readouts via reverse-phase protein microarray revealing a significant attenuation of key UV-induced proteomic changes by resatorvid in chronically treated high-risk SKH-1 skin prior to tumorigenesis. Taken together, our data identify TLR4 as a novel molecular target for topical photochemoprevention of NMSC. Cancer Prev Res; 11(5); 265-78. ©2018 AACRSee related editorial by Sfanos, p. 251.

Dataset Information

Are FDA-Approved Sunscreen Components Effective in Preventing Solar UV-Induced Skin Cancer?

Publications

Are FDA-Approved Sunscreen Components Effective in Preventing Solar UV-Induced Skin Cancer?

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