title: Dose-response on the chemopreventive effects of sarcophine-diol on UVB-induced skin tumor development in SKH-1 hairless mice.
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/cm(2) 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/cm(2). 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/cm(2)). 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.
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Guillermo
authors.affiliation: ACEA Bio Ltd., Hangzhou 310030, Zhejiang, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Radhey S
authors.initials: RS
authors.lastname: Kaushik
authors.affiliation: Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zeman
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Ahmed
authors.affiliation: College of Pharmacy, Qatar University, Doha 02713, Qatar.
authors.forename: Sherief
authors.initials: S
authors.lastname: Khalifa
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Hesham
authors.initials: H
authors.lastname: Fahmy
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Chandradhar
authors.initials: C
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013472:Sunlight / Q000009:adverse effects*; D014466:Ultraviolet Rays; D015430:Weight Gain / Q000528:radiation effects
chemical_list: D016588:Anticarcinogenic Agents; D004224:Diterpenes; D018809:Proliferating Cell Nuclear Antigen; C573078:sarcophine-diol
keywords: SKH-1 mice; UVB radiation; chemopreventive agent; sarcophine-diol; skin cancer