| Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia in vitro. | |
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MedLine Citation:
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PMID: 15911099 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J Subhashini; S V K Mahipal; P Reddanna |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-12-13 |
Journal Detail:
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Title: Cancer letters Volume: 224 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2005 Jun |
Date Detail:
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Created Date: 2005-05-24 Completed Date: 2005-07-19 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 31-43 Citation Subset: IM |
Affiliation:
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Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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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:
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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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