| Cycling B-CLL cells are highly susceptible to inhibition of the proteasome: involvement of p27, early D-type cyclins, Bax, and caspase-dependent and -independent pathways. | |
| | |
MedLine Citation:
|
PMID: 12644019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: Although peripheral blood B-CLL cells are arrested in G0 phase of the cell cycle, a proliferating pool of cells in proliferation centers might be involved in disease progression. We have previously described an in vitro model of this proliferating pool of cells using B-CLL cells stimulated with immunostimulatory oligonucleotides (CpG-ODN) and interleukin-2. Lactacystin is a specific inhibitor of the proteasome and is a potent apoptosis inductor in resting peripheral B-CLL cells. In the present study, we investigated the effect of proteasome inhibition in proliferating B-CLL cells. METHODS: The effect of proteasome inhibition was analyzed using thymidine incorporation, annexin V assays, and TUNEL staining. Immunoblots were performed to evaluate expression of proteins involved in cell cycle and apoptosis regulation. RESULTS: Lactacystin blocked cell cycle progression in activated B-CLL cells and inhibited degradation of p27. Upregulation of cyclin D2 and D3 in activated B-CLL cells was inhibited while the expression of cdk2, cdk4, and cyclin E remained unchanged. Activated B-CLL cells were more susceptible to apoptosis induction as compared to resting B-CLL cells. Apoptosis induction was accompanied by cleavage of Bax, procaspase 8, procaspase 9, and procaspase 3. However, a broad-spectrum caspase inhibitor (z-VAD.fmk) only partially inhibited cell death although DNA degradation was completely inhibited. CONCLUSION: Proteasome inhibition is highly effective in proliferating B-CLL cells and induces apoptosis using a caspase-dependent and -independent pathway. |
| | |
Authors:
|
Christian Bogner; Folker Schneller; Susanne Hipp; Ingo Ringshausen; Christian Peschel; Thomas Decker |
Related Documents
:
|
17476329 - Cyclin e and cdk2 repress the terminal differentiation of quiescent cells after asymmet... 11453659 - Bmp-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(cip1) and... 10558879 - Effect of arsenic trioxide on cell cycle arrest in head and neck cancer cell line pci-1. 15575889 - Evaluation of cyclin d1 expression and its subcellular distribution in mouse tissues. 16287839 - The hematopoietic transcription factor aml1 (runx1) is negatively regulated by the cell... 12402499 - Cdks and ckis: molecular targets for tissue remodelling. 22019849 - Targeted anticancer prodrug with mesoporous silica nanoparticles as vehicles. 9242269 - Anticipatory time intervals of head-direction cells in the anterior thalamus of the rat... 16180049 - Establishment of immortalized schwann cells from sandhoff mice and corrective effect of... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Experimental hematology Volume: 31 ISSN: 0301-472X ISO Abbreviation: Exp. Hematol. Publication Date: 2003 Mar |
Date Detail:
|
Created Date: 2003-03-19 Completed Date: 2003-05-09 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0402313 Medline TA: Exp Hematol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 218-25 Citation Subset: IM |
Copyright Information:
|
Copyright 2003 International Society for Experimental Hematology |
Affiliation:
|
IIIrd Department of Medicine, Technical University of Munich, Munich, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcysteine
/
analogs & derivatives*,
pharmacology Apoptosis / drug effects Caspases / drug effects, metabolism Cell Cycle* Cell Cycle Proteins / drug effects* Cell Division / drug effects Cyclin-Dependent Kinase Inhibitor p27 Cyclins / drug effects Cysteine Endopeptidases Cysteine Proteinase Inhibitors / pharmacology* Dose-Response Relationship, Drug Humans Leukemia, Lymphocytic, Chronic, B-Cell / pathology* Multienzyme Complexes / antagonists & inhibitors* Proteasome Endopeptidase Complex Proto-Oncogene Proteins / drug effects, metabolism Proto-Oncogene Proteins c-bcl-2* Tumor Suppressor Proteins / drug effects bcl-2-Associated X Protein |
| Chemical | |
Reg. No./Substance:
|
0/BAX protein, human; 0/Cell Cycle Proteins; 0/Cyclins; 0/Cysteine Proteinase Inhibitors; 0/Multienzyme Complexes; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Proteins; 0/bcl-2-Associated X Protein; 133343-34-7/lactacystin; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 616-91-1/Acetylcysteine; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The role of mitochondrial-mediated apoptosis in a myelodysplastic syndrome secondary to congenital d...
Next Document: Hammerhead ribozyme-mediated cleavage of the fusion transcript NPM-ALK associated with anaplastic la...