Chemopreventive Activity of Azadirachta indica on Two-stage Skin Carcinogenesis in Murine Model

The present study reports the chemopreventive activity of aqueous Azadirachta indica leaf extract (AAILE) in a murine two-stage skin carcinogenesis model. Skin tumors were induced by topical application of 7,12-dimethylbenz(a) anthracene (DMBA) (500 nmol/100 mu L for 2 weeks) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 mu L of acetone, twice weekly) as a promoter. Male LACA mice were divided into four groups: control, DMBA/TPA, AAILE and AAILE + DMBA/TPA. AAILE was administered orally at a dose level of 300 mg/kg body weight thrice a week for 20 weeks. 100% tumor incidence was observed in the DMBA/TPA treated animals, whereas the AAILE + DMBA treated animals exhibited a tumor incidence of 58.3% only. A significant reduction in the mean tumor burden (54.5%) and mean tumor volume (45.6%) was observed in the mice that received AAILE along with DMBA/TPA. Topical application of DMBA/TPA to the skin resulted in well-developed carcinomas associated with decreased expression of pro-apoptotic protein such as caspase 3 and enhanced expression of antiapoptotic protein such as bcl-2 when compared with the control counterparts. However, adminstration of AAILE inhibited skin carcinogenesis with induction of pro-apoptotic proteins such as bax, caspase 3, caspase 9 and inhibition of antiapoptotic proteins such as bcl-2. These results suggest that the induction of apoptosis may be one of the mechanisms underlying the chemopreventive effects of A. indica. Copyright (c) 2010 John Wiley & Sons, Ltd.