Document Detail


Calpain inhibition stimulates caspase-dependent apoptosis induced by taxol in NIH3T3 cells.
MedLine Citation:
PMID:  17145055     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (Delta Psi m) which could be responsible of Ca(2+) 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.
Authors:
David Piñeiro; M Elena Martín; Natalia Guerra; Matilde Salinas; Víctor M González
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-26
Journal Detail:
Title:  Experimental cell research     Volume:  313     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-12     Completed Date:  2007-03-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  369-79     Citation Subset:  IM    
Affiliation:
Servicio de Bioquímica-Investigación, Hospital Ramón y Cajal, Ctra Colmenar km 9,100, 28034 Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis* / drug effects
Calcium / analysis,  metabolism
Calpain / antagonists & inhibitors,  physiology*
Caspase 3 / antagonists & inhibitors,  physiology*
Cysteine Proteinase Inhibitors / pharmacology
Cytoplasm / chemistry,  metabolism
Dipeptides / pharmacology
Membrane Potential, Mitochondrial / drug effects
Mice
NIH 3T3 Cells
Paclitaxel / pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Cysteine Proteinase Inhibitors; 0/Dipeptides; 33069-62-4/Paclitaxel; 7440-70-2/Calcium; 88191-84-8/calpain inhibitor III; EC 3.4.22.-/Calpain; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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