| Autor: |
Zisterer DM; Biochemistry Department, Trinity College Dublin, Dublin 2, Ireland. dzistrer@tcd.ie, McGee MM, Campiani G, Ramunno A, Fattorusso C, Nacci V, Lawler M, Williams DC |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical Society transactions [Biochem Soc Trans] 2001 Nov; Vol. 29 (Pt 6), pp. 704-6. |
| DOI: |
10.1042/0300-5127:0290704 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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