Modulation of xenobiotic-metabolizing enzymes by ethanolic neem leaf extract during hamster buccal pouch carcinogenesis.
J Exp Clin Cancer Res. 2005 Jun;24(2):223-30. PMID: 16110755
Dept. of Biochemistry, Faculty of Science Annamalai University, Annamalainagar, India.
Chemoprevention by medicinal plants is a promising approach for controlling cancer. There is substantial evidence to indicate that chemopreventive agents exert their anticarcinogenic effects by modulation of phase I and phase II xenobiotic-metabolizing enzymes. Therefore, we examined the chemopreventive potential of ethanolic neem leaf extract (ENLE) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into four groups of six animals each. The right buccal pouches of animals in Group I were painted with 0.5 per cent DMBA in liquid paraffin three times per week. Animals in Group 2 painted with DMBA as in group 1, received in addition, intragastric administration of ENLE at a concentration of 200 mg/kg bw three times per week on days alternate to DMBA application. Group 3 was given ENLE alone. Animals in Group 4 served as controls. All animals were killed after an experimental period of 14 weeks. Five out of six hamsters painted with DMBA alone developed squamous cell carcinomas in the buccal pouch. The HBP tumours showed an increase in phase I carcinogen activation (cytochrome P450 and b5) and phase II detoxification enzyme (glutathione-S-transferase, DT-diaphorase and NADPH-diaphorase) activities. In the liver of tumour-bearing animals, enhanced cytochrome P450 and b5 levels were accompanied by a decrease in phase II detoxification enzyme activities. Administration of ENLE effectively suppressed DMBA-induced HBP tumours, decreased cytochrome P450 and b5 levels, and enhanced phase II enzyme activities in the pouch and liver. Our results suggest that the modulation of DMBA metabolism is a possible mechanism for the chemopreventive effects of ethanolic neem leaf extract.