Chemoprevention of rat mammary carcinogenesis by azadirachta indica leaf fractions: modulation of hormone status, xenobiotic-metabolizing enzymes, oxidative stress, cell proliferation and apoptosis
Chemoprevention of rat mammary carcinogenesis by azadirachta indica leaf fractions: modulation of hormone status, xenobiotic-metabolizing enzymes, oxidative stress, cell proliferation and apoptosis
Date
2009
Authors
Vinothini, G.
Manikandan, P.
Anandan, R.
Nagini, S.
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Abstract
We evaluated the chemopreventive potential of the ethyl acetate fraction (EAF) and methanolic fraction
(MF) of Azadirachta indica (neem) leaf on 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary
carcinogenesis. Estradiol and estrogen receptor status, xenobiotic-metabolizing enzyme activities,
redox status, DNA and protein modifications, and the expression of cell proliferation, and apoptosis
related proteins in the mammary gland and liver were used as biomarkers of chemoprevention. Administration
of both EAF and MF at a dose of 10 mg/kg bw effectively suppressed tumour incidence. Chemoprevention
by neem leaf fractions was associated with modulation of hormone and receptor status,
xenobiotic-metabolising enzymes, and lipid and protein oxidation, with upregulation of antioxidants,
inhibition of oxidative DNA damage, protein modification, and cell proliferation, and induction of apoptosis.
However EAF rich in constituent phytochemicals was more effective than MF in modulating multiple
molecular targets. These results provide evidence for the chemopreventive efficacy of neem leaf
fractions in the rat mammary tumour model.
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Citation
Food Chem. Toxicol. 47(8):1852-1863