Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis
| Autor: | Ying Huang, Cyrus Parsa, Sherry Liang, Robert Orlando, Kevin M. Huang, Kristan H. Cleveland, Bradley T. Andresen, Etuajie Oiyemhonlan, Steven Yeung, Frank L. Meyskens |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Keratinocytes Cancer Research Neoplasms Radiation-Induced Skin Neoplasms Carcinogenesis Ultraviolet Rays Clinical Sciences Oncology and Carcinogenesis Carbazoles Inflammation Pyrimidine dimer Pharmacology medicine.disease_cause Administration Cutaneous Propanolamines 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Anticarcinogenic Agents Humans Neoplastic transformation Oncology & Carcinogenesis Carvedilol Mice Hairless Epidermal Growth Factor Chemistry NF-kappa B Hyperplasia medicine.disease Transcription Factor AP-1 Disease Models Animal 030104 developmental biology Cell Transformation Neoplastic HEK293 Cells Oncology Epidermal Cells 030220 oncology & carcinogenesis Tumor promotion Female Skin cancer medicine.symptom Epidermis Sunscreening Agents medicine.drug |
| Zdroj: | Huang, Kevin M; Liang, Sherry; Yeung, Steven; Oiyemhonlan, Etuajie; Cleveland, Kristan H; Parsa, Cyrus; et al.(2017). Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis.. Cancer prevention research (Philadelphia, Pa.), 10(10), 598-606. doi: 10.1158/1940-6207.capr-17-0132. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/9x959695 Huang, Kevin M; Liang, Sherry; Yeung, Steven; Oiyemhonlan, Etuajie; Cleveland, Kristan H; Parsa, Cyrus; et al.(2017). Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis.. Cancer prevention research (Philadelphia, Pa.), 10(10), 598-606. doi: 10.1158/1940-6207.capr-17-0132. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/5z67p1hp |
| ISSN: | 1940-6215 |
| Popis: | In previous studies, the β-blocker carvedilol inhibited EGF-induced epidermal cell transformation and chemical carcinogen-induced mouse skin hyperplasia. As exposure to ultraviolet (UV) radiation leads to skin cancer, the present study examined whether carvedilol can prevent UV-induced carcinogenesis. Carvedilol absorbs UV like a sunscreen; thus, to separate pharmacological from sunscreen effects, 4-hydroxycarbazole (4-OHC), which absorbs UV to the same degree as carvedilol, served as control. JB6 P+ cells, an established epidermal model for studying tumor promotion, were used for evaluating the effect of carvedilol on UV-induced neoplastic transformation. Both carvedilol and 4-OHC (1 μmol/L) blocked transformation induced by chronic UV (15 mJ/cm2) exposure for 8 weeks. However, EGF-mediated transformation was inhibited by only carvedilol but not by 4-OHC. Carvedilol (1 and 5 μmol/L), but not 4-OHC, attenuated UV-induced AP-1 and NF-κB luciferase reporter activity, suggesting a potential anti-inflammatory activity. In a single-dose UV (200 mJ/cm2)-induced skin inflammation mouse model, carvedilol (10 μmol/L), applied topically after UV exposure, reduced skin hyperplasia and the levels of cyclobutane pyrimidine dimers, IL1β, IL6, and COX-2 in skin. In SKH-1 mice exposed to gradually increasing levels of UV (50–150 mJ/cm2) three times a week for 25 weeks, topical administration of carvedilol (10 μmol/L) after UV exposure increased tumor latency compared with control (week 18 vs. 15), decreased incidence and multiplicity of squamous cell carcinomas, while 4-OHC had no effect. These data suggest that carvedilol has a novel chemopreventive activity and topical carvedilol following UV exposure may be repurposed for preventing skin inflammation and cancer. Cancer Prev Res; 10(10); 598–606. ©2017 AACR. |
| Databáze: | OpenAIRE |
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