Chemopreventive effects of α-santalol on ultraviolet B radiation-induced skin tumor development in SKH-1 hairless mice

• Published in: Carcinogenesis (New York) 2006-09, Vol.27 (9), p.1917-1922
• Main Authors: Dwivedi, Chandradhar, Valluri, Hima B., Guan, Xiangming, Agarwal, Rajesh
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents - pharmacology; Carcinogens; Drugs, Chinese Herbal - pharmacology; Female; Mice; Mice, Hairless; Models, Chemical; Neoplasms, Radiation-Induced - prevention & control; Ornithine Decarboxylase - metabolism; Sesquiterpenes - pharmacology; Skin Neoplasms - chemically induced; Skin Neoplasms - etiology; Skin Neoplasms - prevention & control; Ultraviolet Rays
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgl058

Recent studies from our laboratory have shown the chemopreventive effects of α-santalol against 7,12-dimethylbenzanthracene (DMBA) initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted skin tumor development in mice. The objective of the present investigation was to study the effects of α-santalol on ultraviolet B (UVB) radiation-induced skin tumor development and UVB-caused increase in epidermal ornithine decarboxylase (ODC) activity in female hairless SKH-1 mice. For the tumor studies, 180 mice were divided into three groups of 60 mice each, and each group was divided into two subgroups of 30 mice. The first subgroup served as control and was treated topically on the dorsal skin with acetone. The second subgroup served as experimental and was treated topically on the dorsal skin with α-santalol (5%, w/v in acetone). The tumorigenesis in the first group was initiated with UVB radiation and promoted with TPA; in the second group it was initiated with DMBA and promoted with UVB radiation; and in the third group it was both initiated and promoted with UVB radiation. In each case, the study was terminated at 30 weeks. Topical application of α-santalol significantly (P < 0.05) decreased tumor incidence and multiplicity in all the three protocols, suggesting its chemopreventive efficacy against UVB radiation-caused tumor initiation, tumor promotion and complete carcinogenesis. In a short-term biochemical study, topical application of α-santalol also significantly (P < 0.05) inhibited UVB-induced epidermal ODC activity. Together, for the first time, our findings suggest that α-santalol could be a potential chemopreventive agent against UVB-induced skin tumor development and, therefore, warrants further investigations.