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1.
Mol Cell Biochem ; 377(1-2): 163-76, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23397134

RESUMO

Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world. HCC's limited treatment remedies and the poor prognosis emphasize the importance in developing an effective chemoprevention for this disease. Here, we investigated the molecular mechanisms involved in the chemoprevention of silymarin in N-nitrosodiethylamine (NDEA)-induced rat model of HCC. Liver of the rats treated with NDEA showed higher proliferation index and glycoconjugates. NDEA treatment also increased the level of anti-apoptotic proteins with simultaneous decrease in the level of pro-apoptotic proteins along with increased accumulation of Cytochrome c in mitochondria. The carcinogenic insult also increased microsomal phase I metabolizing enzymes with a simultaneous decrease in the Phase II detoxifying enzyme glutathione-S-transferase (GST). Whereas dietary silymarin administration along with NDEA treatment significantly decreased the proliferation and down regulated the expression of anti-apoptotic proteins with simultaneously increased expression of pro-apoptotic proteins along with the release of Cytochrome c to cytosol there by activating the intrinsic apoptotic pathway. Silymarin administration also decreased the level of glycoproteins and activated the phase II detoxifying enzyme GST. These results demonstrate that suppression of HCC by silymarin in vivo involves inhibition of proliferation, activation of apoptosis, and efficient detoxification.


Assuntos
Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Silimarina/administração & dosagem , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Células Cultivadas , Ciclina D1/metabolismo , Suplementos Nutricionais , Ensaios de Seleção de Medicamentos Antitumorais , Glicoproteínas/metabolismo , Hexosaminas/metabolismo , Hexoses/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Desintoxicação Metabólica Fase II , Proteínas Associadas aos Microtúbulos/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , Ácidos Siálicos/metabolismo , Survivina , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/metabolismo
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