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Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice
Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA
ACEA Bio Ltd., Hangzhou 310030, Zhejiang, China
Department of Biology/Microbiology, South Dakota State University, Brookings, SD 57007, USA
Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA
Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
College of Pharmacy, Qatar University, Doha 02713, Qatar
* Author to whom correspondence should be addressed.
Received: 31 July 2012; in revised form: 17 September 2012 / Accepted: 17 September 2012 / Published: 24 September 2012
Abstract: Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm2 UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm2. This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle), and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone) 1 h before UVB radiation (30 mJ/cm2). The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.
Keywords: sarcophine-diol; skin cancer; chemopreventive agent; SKH-1 mice; UVB radiation
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Guillermo, R.F.; Zhang, X.; Kaushik, R.S.; Zeman, D.; Ahmed, S.A.; Khalifa, S.; Fahmy, H.; Dwivedi, C. Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice. Mar. Drugs 2012, 10, 2111-2125.
Guillermo RF, Zhang X, Kaushik RS, Zeman D, Ahmed SA, Khalifa S, Fahmy H, Dwivedi C. Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice. Marine Drugs. 2012; 10(9):2111-2125.
Guillermo, Ruth F.; Zhang, Xiaoying; Kaushik, Radhey S.; Zeman, David; Ahmed, Safwat A.; Khalifa, Sherief; Fahmy, Hesham; Dwivedi, Chandradhar. 2012. "Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice." Mar. Drugs 10, no. 9: 2111-2125.