| Factors affecting topotecan-induced programmed cell death: adhesion protects cells from apoptosis and impairs cleavage of poly(ADP-ribose)polymerase. | |
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MedLine Citation:
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PMID: 9187115 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have evaluated the influence of anchorage status together with endogenous levels of bcl-2 family members on the ability of the topoisomerase I inhibitor, topotecan (TPT), to induce programmed cell death (PCD) in human colon, breast, lymphoid, and cervical cancer cell lines. As part of this study, we assessed the use of measuring poly(ADP-ribose) polymerase (PARP) cleavage by Western blot, as an index of apoptosis, relative to measuring chromatin condensation by acridine orange analysis. Our results show a strong correlation between both assays, indicating that PARP cleavage is an accurate method to examine PCD. We have encountered a strong association between cell attachment and sensitivity to TPT-induced PCD. Cells growing attached to flasks appear to be relatively more resistant than suspension-growing cells in spite of endogenous bcl-2, bax, or bcl-x levels. Furthermore, we demonstrate that interference with attachment status alters the sensitivity of cells to TPT-induced PCD. Although cell attachment to ProNectin F confers protection against TPT-induced chromatin condensation and cleavage of PARP, cell detachment by poly(2-hydroxyethyl methacrylate) stimulates TPT-induced PCD and PARP cleavage. |
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Authors:
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C M Whitacre; N A Berger |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 57 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1997 Jun |
Date Detail:
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Created Date: 1997-07-10 Completed Date: 1997-07-10 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2157-63 Citation Subset: IM |
Affiliation:
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Department of Medicine and Cancer Center, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4937, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis* Blotting, Western Camptothecin / analogs & derivatives*, pharmacology Cell Adhesion Chromatin / metabolism Fibronectins / metabolism Hela Cells Humans Methacrylates / pharmacology Neoplasms / pathology* Poly(ADP-ribose) Polymerases / immunology, metabolism* Proto-Oncogene Proteins / immunology, metabolism Proto-Oncogene Proteins c-bcl-2 / immunology, metabolism Recombinant Proteins / metabolism Topotecan Tumor Cells, Cultured bcl-2-Associated X Protein |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA51183/CA/NCI NIH HHS; P30 CA43703/CA/NCI NIH HHS; U01 CA63200/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/BAX protein, human; 0/Chromatin; 0/Fibronectins; 0/Methacrylates; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Recombinant Proteins; 0/bcl-2-Associated X Protein; 123948-87-8/Topotecan; 137599-18-9/ProNectin F; 7689-03-4/Camptothecin; 868-77-9/hydroxyethyl methacrylate; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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