RESUMEN
We evaluated the chemopreventive potential of Azadirachta indica (neem) leaf fractions based on in vitro antioxidant assays, and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. In addition we also identified the major constituents in neem leaf fractions by HPLC. Analysis of the free radical scavenging activities and reducing potential of crude ethanolic extract (CEE), ethyl acetate fraction (EAF) and methanolic fraction (MF) of neem leaf revealed a concentration-dependent increase in antioxidant potential that was in the order EAF>MF>CEE. Administration of neem leaf fractions reduced the incidence of DMBA-induced HBP carcinomas at a lower concentration compared to the crude extract. Chemoprevention by neem leaf fractions was associated with modulation of phase I and phase II xenobiotic-metabolising enzymes, lipid and protein oxidation, upregulation of antioxidant defences, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. However, EAF was more effective than MF in terms of antiproliferative and antiangiogenic effects, and expression of CYP isoforms. The greater efficacy of EAF may be due to higher content of constituent phytochemicals as revealed by HPLC analysis. The results of the present study suggest that the antioxidant properties of neem leaf fractions may be responsible for modulating key hallmark capabilities of cancer cells such as cell proliferation, angiogenesis and apoptosis in the HBP carcinogenesis model.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Azadirachta/química , Carcinoma de Células Escamosas/prevención & control , Neoplasias de la Boca/prevención & control , Fitoterapia , Extractos Vegetales/uso terapéutico , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Inhibidores de la Angiogénesis/análisis , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Biomarcadores , Carcinógenos/toxicidad , Carcinoma de Células Escamosas/inducido químicamente , División Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Cricetinae , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/metabolismo , Masculino , Mesocricetus , Neoplasias de la Boca/inducido químicamente , Extractos Vegetales/análisis , Hojas de la Planta/químicaRESUMEN
Combination chemoprevention is a promising approach for oral cancer prevention. The authors evaluated the combined chemopreventive effects of bovine milk lactoferrin (bLF) and black tea polyphenols (Polyphenon-B) in a clinically relevant in vivo model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Although dietary administration of bLF and Polyphenon-B alone significantly reduced the tumor incidence, combined administration of bLF and polyphenon-B was more effective in inhibiting DMBA-induced genotoxicity and development of HBP carcinomas by modulation of carcinogen-metabolizing enzymes and cellular redox status. These results suggest that a "designer item" approach will be useful for human oral cancer prevention strategies.