Calpain inhibition stimulates caspase-dependent apoptosis induced by taxol in NIH3T3 cells

  1. Piñeiro, David 1
  2. Martín, M. Elena 1
  3. Guerra, Natalia
  4. Salinas, Matilde
  5. González, Víctor M.
  1. 1 Servicio de Bioquímica–Investigación, Hospital Ramón y Cajal, Ctra. Colmenar km 9,100, 28034 Madrid, Spain
Revista:
Experimental Cell Research

ISSN: 0014-4827

Año de publicación: 2007

Volumen: 313

Número: 2

Páginas: 369-379

Tipo: Artículo

DOI: 10.1016/J.YEXCR.2006.10.020 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Experimental Cell Research

Resumen

Taxol is an anticancer drug that triggers apoptosis in a wide spectrum of cancers such as ovarian, breast, lung, head and neck, and bladder carcinoma by both caspase-dependent and -independent apoptosis mechanisms. However, the exact signaling pathways involved in taxol-induced apoptosis strongly depend on the cellular background and they are not completely established yet. In this study we demonstrate that taxol induces caspase-3-independent apoptosis in NIH3T3 cells by a calpain-mediated mechanism. Taxol treatment produced changes in the mitochondrial membrane potential (ΔΨm) which could be responsible of Ca2+ release from the mitochondria and the consequent calpain activation. Interestingly, we show that calpain produced proteolysis of caspase-3 and demonstrate that, accordingly, calpain inhibition increased taxol-induced apoptosis. In addition, we reveal that poly (ADP-ribose) polymerase (PARP) was processed by calpain in taxol-treated cells and by caspase-3 after calpain inhibition. In conclusion, these results demonstrate for the first time that calpain could play an important role modulating taxol-induced apoptosis. Further studies are needed to address the potentiality of inducing apoptosis by a combined use of taxol and calpain inhibitors in cells with increased calpain activity.

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