Nuclear caspase-3 and capase-7 activation, and Poly(ADP-ribose) polymerase cleavage are early events in camptothecin-induced apoptosis |
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Authors: | Á. Rodríguez-Hernández G. Brea-Calvo D. J. M. Fernández-Ayala M. Cordero P. Navas J. A. Sánchez-Alcázar |
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Affiliation: | (1) Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Sevilla, 41013, Spain;(2) Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Carretera de Utrera Km 1, Sevilla, 41013, Spain |
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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. An erratum to this article is available at . |
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Keywords: | apoptosis camptothecin cancer cells nuclear caspases PARP |
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