| Cell-killing by paclitaxel in a metastatic murine melanoma cell line is mediated by extensive telomere erosion with no decrease in telomerase activity. | |
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MedLine Citation:
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PMID: 9864398 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of this study was to investigate and compare the effects of paclitaxel and its water-soluble conjugates (sodium-pentetic acid-paclitaxel; polyethylene glycol-paclitaxel, and poly[L-glutamic acid]-paclitaxel) on chromosome morphology and induction of apoptosis in a metastatic murine melanoma cell line (K1735 clone X-21). For this, murine melanoma cells were treated continuously for 72 h with three concentrations (1.2 microM, 2.4 microM, and 4.8 microM) of each of paclitaxel, and conjugates. Another set of cells were pulse-treated at 2.4 microM, 4.8 microM and 9.6 microM concentrations of each of these drugs for 4 h and the recovered cells were examined after 72 h. Control cultures received only the solvents (dimethyl sulfoxide or water). Our results showed a significant increase in the frequencies of telomeric associations, chromosome aberrations, polyploidization, distorted and disintegrated chromosome morphology, and reduced telomeric signal intensity by fluorescence in situ hybridization, in treated cultures as compared to the controls. However, we detected no change in telomerase activity. In addition, the majority of interphase nuclei in treated cells showed apoptotic bodies, with chromatin condensation. These in vitro results suggest that cell death induced by paclitaxel and its water-soluble conjugates is due to the loss of telomeric repeats, as shown by reduced signal flourescence and increased telomeric associations. |
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Authors:
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A S Multani; C Li; M Ozen; A S Imam; S Wallace; S Pathak |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Oncology reports Volume: 6 ISSN: 1021-335X ISO Abbreviation: Oncol. Rep. Publication Date: 1999 Jan-Feb |
Date Detail:
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Created Date: 1999-03-22 Completed Date: 1999-03-22 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: GREECE |
Other Details:
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Languages: eng Pagination: 39-44 Citation Subset: IM |
Affiliation:
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Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents, Phytogenic / administration & dosage, pharmacology* Apoptosis / drug effects Cell Nucleus / pathology Chromosomes / drug effects, ultrastructure Dose-Response Relationship, Drug Humans In Situ Hybridization, Fluorescence Interphase Melanoma, Experimental / enzymology, pathology* Mice Micronucleus Tests Neoplasm Metastasis Neoplasm Proteins / analysis* Paclitaxel / administration & dosage, analogs & derivatives, pharmacology* Polyploidy Telomerase / analysis* Telomere / drug effects*, ultrastructure Tumor Cells, Cultured / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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R29-CA74819/CA/NCI NIH HHS; RRO 499901/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Neoplasm Proteins; 33069-62-4/Paclitaxel; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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