Document Detail


The effect of vinca alkaloid anticancer drug, vinorelbine, on chromatin and histone proteins in solution.
MedLine Citation:
PMID:  19394329     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vinorelbine (navelbin) belongs to vinca alkaloid anticancer drugs family with a broad spectrum of selective activity against mitotic microtubules. The present study is the first report demonstrating chromatin components as a novel target for vinorelbine in hepatocytes. The interaction was carried out in solution, employing fluorescence, UV spectroscopy and thermal denaturation techniques. Fluorescence emission spectra represented quenching of DNA chromospheres with drug and decreased fluorescence emission intensity in a dose-dependent manner. Binding of vinorelbine to chromatin induced very high hypochromicity and shifted DNA melting temperature to lower Tm. Vinorelbine binds to histone proteins with very high affinity when compared with the interaction of DNA intercalator anticancer drug, daunomycin, and the globular domain of the histones is considered as a main drug binding site. The results also showed that in the presence of vinorelbine, the absorbance of chromatin at 260 nm was decreased and the binding pattern was similar to daunomycin-chromatin complex. The results for the first time suggest that apart from tubulins, chromatin components can also be considered as a new target for this anticancer drug.
Authors:
Azra Rabbani-Chadegani; Elham Chamani; Zahra Hajihassan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-24
Journal Detail:
Title:  European journal of pharmacology     Volume:  613     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-01     Completed Date:  2009-08-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  34-8     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. rabbani@ibb.ut.ac.ir
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MeSH Terms
Descriptor/Qualifier:
Absorption
Animals
Antineoplastic Agents / metabolism,  pharmacology*
Cattle
Chromatin / drug effects*,  metabolism
DNA / metabolism
Daunorubicin / metabolism
Histones / metabolism*
Microtubules / drug effects,  metabolism
Rats
Solutions
Spectrometry, Fluorescence
Ultraviolet Rays
Vinblastine / analogs & derivatives*,  metabolism,  pharmacology
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Chromatin; 0/Histones; 0/Solutions; 20830-81-3/Daunorubicin; 71486-22-1/vinorelbine; 865-21-4/Vinblastine; 9007-49-2/DNA

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


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