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Biochem Biophys Res Commun ; 435(4): 657-63, 2013 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-23688426

RESUMO

Autophagy is a self-proteolysis process in eukaryotic cells that results in the sequestering of intracellular proteins and organelles in autophagosomes. Activation of autophagy progress continued growth of some tumors, instead extensive autophagy induces cell death. In a previous study, we synthesized a novel tamoxifen derivative, Ridaifen (RID)-B. RID-B induced mitochondria-involved apoptosis even in estrogen receptor (ER)-negative cells. Since tamoxifen induces autophagy other than apoptosis, we treated ER-negative Jurkat cells with RID-B in the present study. RID-B treatment induced apoptosis and LC3 and lysosome colocalization, which results in the formation of autolysosomes. Western blotting revealed that LC3 was converted to LC3-I to LC3-II with RID-B treatment, suggesting that RID-B induced autophagy without ER involvement. Moreover, overexpression of the anti-apoptotic protein Bcl-2 suppressed the RID-B-induced cell death, but not the induction of autophagy. These results presumed that RID-B-induced autophagy is independent of Bcl-2, making RID-B-induced autophagy different from RID-B-induced apoptosis. Since Beclin 1 level is unchanged during RID-B treatment, RID-B induced autophagy pathway is Bcl-2/Beclin1 independent noncanonical pathway.


Assuntos
Autofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pirrolidinas/administração & dosagem , Receptores de Estrogênio/metabolismo , Tamoxifeno/análogos & derivados , Antineoplásicos Hormonais/administração & dosagem , Humanos , Células Jurkat , Tamoxifeno/administração & dosagem
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