Proapoptotic effects of alpha-santalol as possible mechanism of skin cancer prevention

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Skin cancer is the most prevalent of all cancers and its incidence is expected to increase substantially because of increased recreational exposure to sunlight and depletion of the ozone layer. It is estimated that more than one million Americans develop skin cancer every year. Chemoprevention involves the administration of chemical agents to prevent initiation and\or promotion, and\or progression that occurs during neoplastic development. Previous studies from our laboratory have indicated skin cancer chemopreventive effects of α-santalol in chemically induced SENCAR & CD-1 mice and UV-B induced SKH-1 mice. Further studies have shown the possible role of caspase-3 and 8. Objective: To study possible role of apoptotic proteins involved in the prevention of skin tumor development. SKH-1 mice were divided into three groups. Group 1 received acetone (0.1 ml, topical) one hour before UV-B treatments; Group 2 received α-santalol (0.1 ml, 5 % in acetone, topical) one hour before UV-B treatments; and Group 3 received α-santalol (0.1 ml, 5 % in acetone, topical) immediately after UV-B treatments. In long-term experiment the promotion phase was carried out for 30 weeks. The duration of short-term experiment 1 week. After the end the experiments, mice were sacrificed and dorsal skin samples were collected. The proteins from the skin samples were extracted and further used for SDS-PAGE and Western blot using specific antibodies against caspase-3 and 8. The cleaved caspase-3 levels were increased by 472 and 220% in Group 2 and 3 respectively when compared to Group 1. The cleaved caspase-8 levels were increased by 265 and 220% in Group 2 and 3 respectively when compared to Group 1. In short term experiment caspase 3 levels were increased by 164 and 144% in Group 2 and 3 respectively when compared to Group 1. Caspase 8 levels were increased by 138 and 127% in Group 2 and 3 respectively when compared to Group 1. Cox 2 levels were decreased by 49 and 55% in Group 2 and 3 respectively when compared to Group 1. Pretreatment with α-santalol reduces UV-B-induced skin cancer development possibly by activating proapoptotic proteins caspase-3 and 8.