Document Detail


Down-regulation of Bcl-2 is associated with cisplatin resistance in human small cell lung cancer H69 cells.
MedLine Citation:
PMID:  15026553     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Overexpression of the anti-apoptotic protein Bcl-2 has been associated with several malignancies, including small cell lung cancer (SCLC). In the present study, we have investigated if Bcl-2 contributes to the emergence of cisplatin resistance in SCLC H69 cells. The ability of cisplatin to induce apoptosis was decreased in H69 cells that acquired resistance to cisplatin (H69/CP). The level of Bcl-2 was, however, substantially reduced in H69/CP cells compared to parental H69 cells. There was little change in Bcl-2 content in H69 cells that were resistant to etoposide (VP-16) or Taxol. Bcl-2 was constitutively phosphorylated at serine 70 in H69 cells but not in H69/CP cells and cisplatin had little effect on Bcl-2 phosphorylation. The level of procaspase-3 was elevated in H69/CP cells but the ability of cisplatin to induce mitochondrial depolarization, caspase-9 activation, and poly(ADP-ribose) polymerase (PARP) cleavage was compromised in H69/CP cells. The level of the anti-apoptotic protein Bcl-x(L) and the pro-apoptotic protein Bax was slightly reduced in H69/CP cells but the ratio of pro-apoptotic and anti-apoptotic Bcl-2 family proteins was not sufficient to explain cellular resistance to cisplatin. These results suggest that the acquisition of cisplatin resistance by H69 cells was not due to an increase in the level/phosphorylation status of the anti-apoptotic protein Bcl-2.
Authors:
Swarajit Kumar Biswas; Jie Huang; Shalini Persaud; Alakananda Basu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  3     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-17     Completed Date:  2004-11-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  327-34     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis
Benzopyrans / pharmacology
Blotting, Western
Carcinoma, Small Cell
Caspase 3
Caspase 9
Caspases / metabolism
Cell Death
Cell Line, Tumor
Cisplatin / pharmacology*
Down-Regulation*
Drug Resistance, Neoplasm*
Enzyme Activation
Enzyme Inhibitors / pharmacology
Etoposide / pharmacology
Flow Cytometry
Humans
Immunoblotting
Lung Neoplasms / pathology*
Membrane Potentials
Mitochondria / pathology
Paclitaxel / pharmacology
Phosphorylation
Poly(ADP-ribose) Polymerases / metabolism
Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Grant Support
ID/Acronym/Agency:
CA85682/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Antineoplastic Agents, Phytogenic; 0/Benzopyrans; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 15663-27-1/Cisplatin; 33069-62-4/Paclitaxel; 33419-42-0/Etoposide; 82-08-6/rottlerin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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


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