The broad-spectrum caspase inhibitor Boc-Asp-CMK induces cell death in human leukaemia cells
In: Toxicology in Vitro, Jg. 22 (2008-08-01), S. 1356-1360
Online
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Zugriff:
Journal URL: http://www.elsevier.com/wps/find/journaldescription.cws_home/800/description Synthetic caspase inhibitors and particularly broad-spectrum caspase inhibitors can prevent cells from death or at least slow down cell death process and abrogate some apoptotic hallmarks [Kitanaka, C., Kuchino, Y., 1999. Caspase-independent programmed cell death with necrotic morphology. Cell Death and Differentiation 6, 508–515]. However, not all synthetic caspase inhibitors diminish cell death. We have found that the broad-spectrum caspase inhibitor Boc-Asp-CMK induced cell death at micromolar concentrations in human leukaemia cells. Interestingly, low concentrations of Boc-Asp-CMK induced cell death with apoptotic hallmarks. Increasing concentrations of Boc-Asp-CMK led to necrotic cell death. The switch between apoptosis and necrosis seemed to depend upon the degree of inhibition of executioner caspases, including caspase-3/7 with Boc-Asp-CMK. Interestingly, caspase-3 processing was not inhibited even for the highest concentration of Boc-Asp-CMK used. We assume, that toxic properties of Boc-Asp-CMK can be attributed to the chloromethylketone residuum in its molecule, as its analogue Boc-Asp-FMK with fluoromethylketone residuum was more than 13 times less toxic. Our results further indicated that toxicity of Boc-Asp-CMK might arise from its interference with mitochondrial metabolism.
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The broad-spectrum caspase inhibitor Boc-Asp-CMK induces cell death in human leukaemia cells
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Autor/in / Beteiligte Person: | Zoumpourlis, Vassilis ; Krumpochova, Petra ; Mlejnek, Petr ; Frydrych, Ivo ; Dolezel, Petr |
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Zeitschrift: | Toxicology in Vitro, Jg. 22 (2008-08-01), S. 1356-1360 |
Veröffentlichung: | Elsevier BV, 2008 |
Medientyp: | unknown |
ISSN: | 0887-2333 (print) |
DOI: | 10.1016/j.tiv.2008.02.017 |
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