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Chemopreventive Effects of Sarcophine-diol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice
Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA
Department of Pharmacology & Chemical Biology and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Department of Veterinary Science, South Dakota State University, Brookings, SD 57007, USA
Department of Biology/Microbiology, South Dakota State University, Brookings, SD 57007, USA
Faculty of Pharmacy, Misr International University, Cairo, Egypt
* Author to whom correspondence should be addressed.
Received: 27 March 2009; in revised form: 16 April 2009 / Accepted: 28 April 2009 / Published: 30 April 2009
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.
Keywords: Chemopreventive agent; Sarcophine-diol; Apoptosis; Skin cancer
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Zhang, X.; Bommareddy, A.; Chen, W.; Hildreth, M.B.; Kaushik, R.S.; Zeman, D.; Khalifa, S.; Fahmy, H.; Dwivedi, C. Chemopreventive Effects of Sarcophine-diol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice. Mar. Drugs 2009, 7, 153-165.
Zhang X, Bommareddy A, Chen W, Hildreth MB, Kaushik RS, Zeman D, Khalifa S, Fahmy H, Dwivedi C. Chemopreventive Effects of Sarcophine-diol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice. Marine Drugs. 2009; 7(2):153-165.
Zhang, Xiaoying; Bommareddy, Ajay; Chen, Wei; Hildreth, Michael B.; Kaushik, Radhey S.; Zeman, David; Khalifa, Sherief; Fahmy, Hesham; Dwivedi, Chandradhar. 2009. "Chemopreventive Effects of Sarcophine-diol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice." Mar. Drugs 7, no. 2: 153-165.