Scientists have discovered a way to cause some cancerous cells to self-destruct. These findings, reported in the October 2006 issue of Nature Chemical Biology, describe the use of a small molecule to 'wake up' the key enzyme -- caspase-3 -- that causes cell death.
Caspase-3 normally exists as a proenzyme, meaning that further processing is required to make the final, active enzyme. This processing is normally performed by other caspases and serves as a signal that something has gone wrong with a cell; it signals that cell death or 'apoptosis' is desired. Paul Hergenrother and colleagues have now used the synthetic compound PAC-1 to trick procaspase-3 into processing itself, generating caspase-3 and causing cell death. They demonstrated, in a variety of cancer cell types, that cell death is correlated with the amount of procaspase-3 present in the cells, with more procaspase-3 resulting in cell death at lower concentrations of PAC-1, while healthy cells remain unaffected.
The variability of procaspase-3 levels in the cell lines tested means that some patients would be more responsive to this therapy than others. As such, this research potentially offers a novel opportunity for individualized cancer therapy.
Paul J Hergenrother (The University of Illinois, Urbana, IL, USA)
Abstract available online.
(C) Nature Chemical Biology press release.
Message posted by: Trevor M. D'Souza