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 µL for 2 weeks) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 µL 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.
Arora
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N
Department of Biophysics, Panjab University, Chandigarh-160014, India.
Koul
A
A
Bansal
M P
MP
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D031601:Azadirachta / Q000737:chemistry*; D002277:Carcinoma / Q000517:prevention & control; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; D010936:Plant Extracts; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate