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.
Highlights
Between two and three million non-melanoma skin cancers occur globally each year
The objective of this study was to determine the chemopreventive effects of SD when applied at different doses (30, 45, 60 μg) on a chronic and low dose (30 mJ/cm2) UVB-induced skin tumor development model in female SKH-1 hairless mice, as this is an experimental model more relevant to human skin cancer development than other investigations using higher UVB doses [28]
There was no significant difference in weight gain among various groups treated with sarcophine-diol or acetone
Summary
Between two and three million non-melanoma skin cancers occur globally each year. American Cancer Society estimates indicated 12,190 deaths from skin cancer in 2012 [2]. The main cause for skin cancer is the excessive exposure to UV radiation from sunlight and/or sunlamps used in indoor tanning [3]. UVB is an important component of solar radiation that acts as a complete carcinogen by initiating and promoting skin cancer [4,5]. UVB is frequently used to induce photocarcinogenesis in animals. UVB radiation induces characteristic DNA damage on skin cells, immunosuppression, and modulation of various signal transduction pathways which can lead to cell proliferation, transformation, and cell death [6,7,8]
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