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Acta Pharmacol Sin ; 29(10): 1233-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18817629

RESUMO

AIM: To investigate the effect of diallyl disulfide (DADS), a component of garlic, on apoptosis in human mammary cancer cell line (MCF-7) and its mechanisms. METHODS: Cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assays. Morphology of apoptotic cells was detected by acridine orange and ethidium bromide staining. Apoptotic cells stained with propidium iodide were examined using flow cytometry. Protein levels were detected by Western blot analysis. RESULTS: DADS inhibited the proliferation of MCF-7 cells and induced the apoptotic ratio to increase rapidly. Cleavage of the caspase-3 and caspase-3 substrate poly(ADP-ribose) polymerase was observed in MCF-7 cells after 24 h of treatment with DADS. When the MCF-7 cells were treated with 200 micromol x L DADS, the stress-activated protein kinase extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase, was inhibited after 6 h; c-Jun N-terminal kinase (JNK), that is stress-activated protein kinase (SAPK), and p38 mitogen-activated protein kinase were activated after 6 h. CONCLUSION: These results suggest that DADS both inhibits the proliferation of MCF-7 cells and induces apoptosis of MCF-7 cells. The mechanisms may include the inhibition of ERK and the activation of the SAPK/JNK and p38 pathways.


Assuntos
Compostos Alílicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Sulfetos/farmacologia , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Feminino , Humanos , MAP Quinase Quinase 4/metabolismo , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Poli(ADP-Ribose) Polimerases/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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