Document Detail


Cell-killing by paclitaxel in a metastatic murine melanoma cell line is mediated by extensive telomere erosion with no decrease in telomerase activity.
MedLine Citation:
PMID:  9864398     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A S Multani; C Li; M Ozen; A S Imam; S Wallace; S Pathak
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncology reports     Volume:  6     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:    1999 Jan-Feb
Date Detail:
Created Date:  1999-03-22     Completed Date:  1999-03-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  GREECE    
Other Details:
Languages:  eng     Pagination:  39-44     Citation Subset:  IM    
Affiliation:
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
R29-CA74819/CA/NCI NIH HHS; RRO 499901/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
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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