Document Detail


Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia in vitro.
MedLine Citation:
PMID:  15911099     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the only non-steroidal anti-inflammatory drug so far which has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis. The molecular mechanism responsible for the anti-cancer effects of celecoxib is not fully understood. There is little data on the potential role of COX-2 in lymphoma pathogenesis. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of celecoxib on human chronic myeloid leukemia cell line, K562 and other hematopoietic cancer cell lines like Jurkat (human T lymphocytes), HL60 (human promyelocytic leukemia) and U937 (human macrophage). Treatment of these cells with celecoxib (10-100 microM) dose-dependently, reduced cell growth with arrest of the cell cycle at G0/G1 phase and induction of apoptosis. Further mechanism of apoptosis induction was elucidated in detail in K562 cell line. Apoptosis was mediated by release of cytochrome c into the cytoplasm and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). This was followed by DNA fragmentation. The level of anti-apoptotic protein Bcl-2 was decreased without any change in the pro-apoptotic Bax. Celecoxib also inhibited NF-kB activation. Celecoxib thus potentiates apoptosis as shown by MTT assay, cytochrome c leakage, PARP cleavage, DNA fragmentation, Bcl-2 downregulation and possibly by inhibiting NF-kB activation.
Authors:
J Subhashini; S V K Mahipal; P Reddanna
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-12-13
Journal Detail:
Title:  Cancer letters     Volume:  224     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-24     Completed Date:  2005-07-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  31-43     Citation Subset:  IM    
Affiliation:
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Cell Proliferation / drug effects*
Cyclooxygenase Inhibitors / pharmacology*
DNA Damage
Down-Regulation
Formazans / toxicity
HL-60 Cells
Humans
Jurkat Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
Macrophages
NF-kappa B / metabolism
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Pyrazoles / pharmacology*
Sulfonamides / pharmacology*
Tetrazolium Salts / toxicity
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Formazans; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-bcl-2; 0/Pyrazoles; 0/Sulfonamides; 0/Tetrazolium Salts; 169590-42-5/celecoxib; 23305-68-2/MTT formazan

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


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