| Caspase-3 mediated feedback activation of apical caspases in doxorubicin and TNF-alpha induced apoptosis. | |
| | |
MedLine Citation:
|
PMID: 17013758 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Aberrant apoptosis has been associated with the development and therapeutic resistance of cancer. Recent studies suggest that caspase deficiency/downregulation is frequently detected in different cancers. We have previously shown that caspase-3 reconstitution significantly sensitized MCF-7 cells to doxorubicin and etoposide. In contrast to the well established role of caspase-3 as an effector caspase, the focus of this study is to delineate caspase-3 induced feedback activation of the apical caspases-2, -8, -9 and -10A in doxorubicin and TNF-alpha induced apoptosis. Using cell-free systems we show that caspases-9 and 2 are the most sensitive, caspase-8 is less sensitive and caspase-10A is the least sensitive to caspase-3 mediated-cleavage. When apoptosis is induced by doxorubicin or TNF-alpha in an intact cell model, cleavage of caspases-8 and -9, but not caspase-2, was markedly enhanced by caspase-3. Caspase-3 mediated-feedback and activation of caspase-8 and -9 in MCF-7/C3 cells is further supported by an increase in the cleavage of caspase-8 and 9 substrates and cytochrome c release. These data indicate that, in addition to its function as an effector caspase, caspase-3 plays an important role in maximizing the activation of apical caspases and crosstalk between the two major apoptotic pathways. The significant impact of caspase-3 on both effector and apical caspases suggests that modulation of caspase-3 activity would be a useful approach to overcome drug resistance in clinical oncology. |
| | |
Authors:
|
Shihe Yang; Ann D Thor; Susan Edgerton; XiaoHe Yang |
Related Documents
:
|
10543748 - Oligonucleotides tethered to a short polyguanylic acid stretch are targeted to macropha... 19861418 - Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis in typ... 14555228 - Anti-apoptotic effect of hiv protease inhibitors via direct inhibition of calpain. 20138848 - Distribution of apoptosis-related proteins in sporadic creutzfeldt-jakob disease. 22510408 - Ribosomal protein s3 interacts with tradd to induce apoptosis through caspase dependent... 8359088 - Intestinal epithelial function: the case for immunophysiological regulation. implicatio... |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: Apoptosis : an international journal on programmed cell death Volume: 11 ISSN: 1360-8185 ISO Abbreviation: Apoptosis Publication Date: 2006 Nov |
Date Detail:
|
Created Date: 2006-11-06 Completed Date: 2007-09-19 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: United States |
Other Details:
|
Languages: eng Pagination: 1987-97 Citation Subset: IM |
Affiliation:
|
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antibiotics, Antineoplastic
/
pharmacology* Apoptosis* Caspase 10 / metabolism Caspase 2 / metabolism Caspase 3 / metabolism* Caspase 8 / metabolism Caspase 9 / metabolism Cell Line, Tumor Cysteine Endopeptidases / metabolism Cytosol / enzymology Doxorubicin / pharmacology* Humans Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Antibiotics, Antineoplastic; 0/CASP10 protein, human; 0/Tumor Necrosis Factor-alpha; 23214-92-8/Doxorubicin; EC 3.4.22.-/CASP2 protein, human; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 10; EC 3.4.22.-/Caspase 2; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Cysteine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: 12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein ...
Next Document: Proteolysis of HIP during apoptosis occurs within a region similar to the BID loop.