Chemoprevention of Skin Cancer by Natural Compounds

Abstract

Skin tumors in humans represent about 30% of all new cancers reported annually (Yusuf et al, 2007); their incidence is expected to increase substantially because of increased recreational exposure to sunlight and depletion of the ozone layer. The main factor incriminated in skin cancer is represented by the ultraviolet radiation, especially type B (UVB), which accounts for 90% of the skin cancer cases (Azis, 2005). Currently, between 2 and 3 million non-melanoma skin cancers and 132.000 melanoma skin cancers occur each year and one in every three cancers diagnosed is a skin cancer according to World Health Organization (WHO, 2004). Further more so, it is estimated that one in five persons will develop a basal cell or squamous cell carcinoma in its life time (Robinson, 2005). The identification of the critical molecular targets and signaling pathways involved in the development of premalign and malign lesions UV-induced and the development of agents that modulate these targets are important steps in the management of skin cancer. In 1894 Paul Gerson Unna established that there was a direct causal relationship between exposure to sunlight and the development of the skin carcinomas (Unna, 1894). The acute exposure to UV radiation leads to erythema, edema, burns, pain, thickening and pigmentation of the skin (Afaq & Mukhtar, 2001) while chronic exposure induces immunosuppression (Aziz, 2005), premature aging (Jurkiewicz et al, 1995; LopezTorres et al, 1998) and skin cancers (Katiyar & Mukhtar, 2001; Katiyar, 2008; Taylor et al, 1990). The sunlight UV spectrum can be separated into three wavelengths: UVA (320-400 nm), UVB (280-320 nm) and UVC (200-280 nm). Primarily UVA and UVB reach the earth’s surface as UVC is filtered out by the ozone layer (Shae & Parrish, 1991). Though the UVB radiations is a small part of UV emissions (4 5%), they are extremely aggresive being 1000 times more carcinogenic than UVA (Bowden, 2004; Mukhtar & Elmets, 1996). UVB directly or through the reactive oxygen species (ROS) affects the genetic material of exposed cells forming photoproducts such as DNA cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone (Afaq et al, 2007) respective 8-oxo-7, 8-dihydroguanine (8-oxo-dG) and 8-hydroxy20-deoxyguanosine (8-OHdG) (Kawachi et al, 2008). Multistage carcinogenesis is a widely accepted hypothesis for the development of skin cancer. Skin carcinogenesis is divided into three stages namely: initiation, promotion and progression. Both UVA and UVB radiation have been shown to be complete carcinogens, capable of initiation, promotion and progression of carcinogenetic process (Aziz et al, 2005; Brash et al, 1996; Elmets et al, 2001). Actually, UV has dual actions in the development of skin cancers, it damages DNA and induces mutations of cellular genes crucial for oncogenesis; it induces immunosuppresion, which prevents tumor rejection by the host. To exert its biological effects, UV must be first absorbed by cellular