Abstract
Sarcophine-diol (SD), one of the structural modifications of sarcophine, has shown chemopreventive effects on 12-dimethylbenz(a)anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor development in female CD-1 mice. The objective of this study was to determine the chemopreventive effects of SD on UVB-induced skin tumor development in hairless SKH-1 mice, a model more relevant to human skin cancer, and to determine the possible mechanisms of action. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into two groups having 27 mice in each group: control and SD treatment. The control group was topically treated with 100 μL acetone and SD treatment group was topically treated with SD (30 μg/100 μL in acetone) 1 hour before each UVB radiation for 32 weeks. Tumor counts were recorded on a weekly basis for 30 weeks. Effects of SD on the expression of caspases were investigated to elucidate the possible mechanism of action. The proteins from epidermal homogenates of experimental mice were used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8 and caspase-9 respectively. TUNEL assay was used for determining DNA fragmented apoptotic cells in situ. Results showed that at the end of experiment, tumor multiplicity in control and SD treatment groups was 25.8 and 16.5 tumors per mouse respectively. Furthermore, Topical treatment of SD induced DNA fragmented apoptotic cells by upgrading the expressions of cleaved caspase-3 and caspase-8. This study clearly suggested that SD could be an effective chemopreventive agent for UVB-induced skin cancer by inducing caspase dependent apoptosis.
Highlights
Non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common malignant neoplasms in human [1]
It has been estimated that more than one million cases of BCC and SCC are diagnosed each year in the US alone [2], which is equivalent to the incidence of malignancies in all other organs combined [3,4]
There was no significant difference in weight gain between control and SD treatment groups throughout the entire experiment
Summary
Non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common malignant neoplasms in human [1]. The UV light that reaches the earth is composed of about 90% UVA and 10% UVB; whereas, UVC does not penetrate the earth's atmosphere [6]. The level of UVB reaching the earth's surface is controlled largely by the amount of ozone in the atmosphere [7,8]. Both UVA and UVB are being studied for their skin cancer-causing potential, but currently UVB is thought to be the most important etiologic factor. UVB can act in mouse skin models as a complete carcinogen, meaning that UVB can function as an initiator as well as a promoter [11,12]
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