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1.
Food Chem Toxicol ; 48(11): 3281-7, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20828598

RESUMEN

Antiproliferative and apoptosis inducing effects of black tea polyphenols (Polyphenon-B) on HepG2 cells in vitro and in a rat hepatocarcinogenesis model in vivo were investigated. Viability of HepG2 cells was evaluated by the MTT assay, and apoptosis by AO-EB and DAPI staining, cell cycle analysis, and annexin V-PI assay. For the in vivo study, male Sprague-Dawley rats treated with dimethylaminoazobenzene (DAB) (0.06%) were used. The expression of Bcl-2 and NF-κB family members were analyzed by immunoblotting. Administration of Polyphenon-B induced dose-dependent inhibition of growth of HepG2 cells and reduced tumor incidence in DAB administered animals. HepG2 cells also exhibited morphological features characteristic of apoptotic cell death. In addition, administration of Polyphenon-B increased the expression of Bax, tBid, Smac/Diablo, cytochrome C, Apaf-1, caspases, and IκB with PARP cleavage, and decreased the expression of Bcl-2, Bcl-xL, pBad, NF-κB, p-IκB-α, IKKß and Ub in both HepG2 cells and in DAB-treated animals. These results provide evidence that Polyphenon-B effectively inhibits proliferation and induces apoptosis both in vitro and in vivo by inhibiting NF-κB, and inducing intrinsic apoptosis by modulating the expression of a network of interrelated molecules eventually culminating in caspase-mediated cell death.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/prevención & control , Neoplasias Hepáticas Experimentales/prevención & control , FN-kappa B/metabolismo , Fenoles/farmacología , Té/química , Animales , Carcinógenos/toxicidad , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/patología , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/patología , Masculino , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , p-Dimetilaminoazobenceno/toxicidad
2.
Anticancer Res ; 29(6): 2301-5, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19528495

RESUMEN

BACKGROUND: The aim of this study was to evaluate the chemopreventive effects of black tea polyphenols (Polyphenon-B) on markers of invasion and angiogenesis during dimethylaminoazobenzene (DAB)-induced hepatocarcinogenesis. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into four groups. The rats in groups 1 and 2 were given 0.06% DAB in the diet for 3 months followed by the normal diet. The rats in group 2 received in addition 0.05% Polyphenon-B in the basal diet. The group 3 animals were given 0.05% Polyphenon-B alone in the basal diet. The group 4 animals served as the control. RESULTS: The dietary administration of DAB induced well-differentiated hepatocellular carcinomas (HCC) that showed increased expression of the markers of invasion, angiogenesis and epigenetic histone deacetylation compared with the controls. The administration of Polyphenon-B significantly reduced the incidence of DAB-induced hepatomas as evidenced by modulation of the markers of invasion (matrix metalloproteinase, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase, TIMP-2, and reversion-inducing cysteine rich protein with Kazal motifs RECK) and angiogenesis (hypoxia inducible factor 1alpha, HIF1alpha, vascular endothelial growth factor, VEGF, and VEGF receptor, VEGFR1) as well as the expression of histone deacetylase HDAC-1. CONCLUSION: The results of the present study provide evidence that Polyphenon-B has potential as a chemopreventive agent.


Asunto(s)
Proteínas Angiogénicas/metabolismo , Modelos Animales de Enfermedad , Histona Desacetilasas/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Glicoproteínas de Membrana/metabolismo , Fenoles/farmacología , Té/química , Proteínas Supresoras de Tumor/metabolismo , Proteínas Angiogénicas/genética , Animales , Western Blotting , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Proteínas Ligadas a GPI , Histona Desacetilasas/genética , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Metaloproteinasas de la Matriz/genética , Glicoproteínas de Membrana/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Supresoras de Tumor/genética
3.
J Med Food ; 10(3): 495-502, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17887944

RESUMEN

The present study was designed to evaluate the protective effects of ethanolic Ocimum sanctum leaf extract against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity, oxidative stress, and imbalance in xenobiotic-metabolizing enzymes. Four different concentrations of ethanolic O. sanctum leaf extract (100, 200, 300, and 400 mg/kg of body weight) were administered to Wistar rats by intragastric intubation for five consecutive days followed by intraperitoneal injection of DMBA (35 mg/kg of body weight) 90 minutes after the final dose of the extract. Administration of DMBA increased bone marrow micronuclei, phase I enzymes, lipid peroxidation, and protein carbonyl formation. This was accompanied by a significant decrease in the activities of phase II detoxification enzymes and antioxidants in the liver, erythrocytes, and bone marrow. Pretreatment with ethanolic O. sanctum leaf extract at a concentration of 300 mg/kg of body weight significantly reduced micronuclei formation and phase I enzymes as well as lipid and protein oxidation with enhanced antioxidant and phase II enzyme activities. The results of the present study suggest that ethanolic O. sanctum leaf extract inhibits DMBA-induced genotoxicity and oxidative stress by modulating xenobiotic-metabolizing enzymes, reducing the extent of lipid and protein oxidation and up-regulating antioxidant defenses.


Asunto(s)
9,10-Dimetil-1,2-benzantraceno/farmacología , Mutación/efectos de los fármacos , Ocimum/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Xenobióticos/metabolismo , Animales , Antioxidantes/análisis , Médula Ósea/ultraestructura , Proteínas Portadoras/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Proteínas de Unión al Hemo , Hemoproteínas/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Hojas de la Planta/química , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar
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