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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Cisplatin inactivation of caspases inhibits death ligand-induced cell death in vitro and fulminant liver damage in mice.

Cisplatin is a platinum-containing chemotherapeutic drug that has been widely used to treat various human cancers. It acts by forming inter- and intracross-links of DNA, which is believed to be a major cause for its therapeutic efficacy. However, little attention has been paid to the effect of cisplatin on death ligand-induced cell death. Here we demonstrate that cisplatin inhibits death ligand-induced cell death in cell lines in a p53-independent manner. This inhibitory effect of cisplatin on cell death is direct, whereby cisplatin forms a complex with caspases leading to their inactivation. The cisplatin-caspase complex is reversed by the addition of reducing agent dithiothreitol, and caspase activity is regained. In addition, cisplatin shows a death-inhibition effect in in vivo animal models of fulminant liver damage induced by Fas activation and lipopolysaccharide-induced liver shock mediated by tumor necrosis factor-alpha. Together, we demonstrate that cisplatin inhibits cell death induced by death ligands in cell lines and in mice through caspase inactivation.[1]

References

  1. Cisplatin inactivation of caspases inhibits death ligand-induced cell death in vitro and fulminant liver damage in mice. Shin, J.N., Seo, Y.W., Kim, M., Park, S.Y., Lee, M.J., Lee, B.R., Oh, J.W., Seol, D.W., Kim, T.H. J. Biol. Chem. (2005) [Pubmed]
 
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