Pyrrolo-1,5-benzoxazepines:a new class of apoptotic agents
Data(s) |
01/11/2001
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Resumo |
<p>Some members of a series of novel pyrrolo-1,5-benzoxazepines (PBOXs) potently induce apoptosis in a number of human cancerous cell lines including HL-60 cells and the drug-resistant chronic myelogenous leukaemia cell line, K562. The apoptotic induction seems to be independent of the mitochondrial peripheral-type benzodiazepine receptor (PBR), which binds these PBOXs with high affinity, due to a lack of correlation between their affinities for the receptor and their apoptotic potencies and their high apoptotic activity in PBR-deficient cells. PBOX-6, a potent member of the series, induces a transient activation of c-Jun N-terminal kinase (JNK) in a dose-dependent manner, which correlates with induction of apoptosis. Expression of a cytoplasmic inhibitor of the JNK signal transduction pathway, Jip-1, prevents JNK activity and significantly reduces the extent of apoptosis induced by PBOX-6. This demonstrates the requirement for JNK in the cellular response to this apoptotic agent. In addition, PBOX-6 activates caspase-3-like proteases in K562 and HL-60 cells. The caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethylketone (z-DEVD-fmk), blocks caspase-3-like protease activity in both cell types but only prevents PBOX-6-induced apoptosis in HL-60 cells, suggesting that the requirement for caspase-3-like proteases in the apoptotic pathway is dependent on the cell type.</p> |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Zisterer , D M , McGee , M M , Campiani , G , Ramunno , A , Fattorusso , C , Nacci , V , Lawler , M , Williams , D C & Lawler , M 2001 , ' Pyrrolo-1,5-benzoxazepines : a new class of apoptotic agents ' Biochemical Society Transactions , vol 29 , no. Pt 6 , pp. 704-6 . |
Palavras-Chave | #Antineoplastic Agents #Apoptosis #Benzazepines #Enzyme Inhibitors #HL-60 Cells #Humans #K562 Cells #Oxazepines #Phosphorylation #Pyrroles |
Tipo |
article |