AI Article Synopsis
- Chemotherapy drugs, like camptothecin, trigger apoptosis in cancer cells through the activation of nuclear caspases (specifically caspases-3 and -7), leading to early biochemical changes.
- This process occurs before the release of cytochrome c and other apoptotic factors, suggesting a different pathway for initiating cell death than previously understood.
- Our study used various laboratory techniques to confirm that damaged DNA can directly activate these nuclear caspases, contributing to a better understanding of how chemotherapy works at a molecular level.
Article Abstract
Chemotherapy-induced apoptosis by DNA-damaging drugs is thought to be generally dependent on the release of cytochrome c and the subsequent activation of caspase-9 and -3. However, the molecular mechanism of how damaged DNA triggers the apoptotic process is not clear. To better understand the mechanisms underlying this process, we examined drug-induced apoptosis in cultured H-460 cells. Using cell fractionation, western blotting, and immunofluorescence assays, we show that the activation of nuclear caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis. Moreover, we demonstrate that these events precede the release of cytochrome c and apoptotic inducing factor, and the activation of caspases 2, 8, 9 and 12. Together our results suggest that drugs acting at the DNA level can initiate apoptosis via nuclear caspase activation.
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| http://dx.doi.org/10.1007/s10495-005-3276-y | DOI Listing |
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