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oai:docta.ucm.es:20.500.14352/983792024-10-07T23:51:24Zcom_20.500.14352_14col_20.500.14352_15

Calpain inhibition stimulates caspase-dependent apoptosis induced by taxol in NIH3T3 cells Piñeiro, David Martín, Elena Guerra Pérez, Natalia Salinas, Matilde González, Victor Apoptosis Calpain Calpain inhibitor Caspase Taxol Ciencias Biomédicas 24 Ciencias de la Vida 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. Ministerio de Sanidad y Consumo (España) Depto. de Genética, Fisiología y Microbiología Fac. de Ciencias Biológicas TRUE pub 2024-02-02T14:59:37Z 2024-02-02T14:59:37Z 2007 journal article VoR https://hdl.handle.net/20.500.14352/98379 0014-4827 10.1016/j.yexcr.2006.10.020 1090-2422 eng Piñeiro, David, et al. «Calpain Inhibition Stimulates Caspase-Dependent Apoptosis Induced by Taxol in NIH3T3 Cells». Experimental Cell Research, vol. 313, n.o 2, enero de 2007, pp. 369-79. https://doi.org/10.1016/j.yexcr.2006.10.020. restricted access application/pdf Elsevier