Document Detail


Everolimus enhances gemcitabine-induced cytotoxicity in bladder-cancer cell lines.
MedLine Citation:
PMID:  22788366     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to determine whether everolimus, a rapamycin derivative, might significantly enhance the cytotoxicity of gemcitabine, an antitumor drug, in two human bladder-cancer cell lines. Human bladder-cancer T24 and 5637 cells were incubated with gemcitabine and everolimus in a range of concentrations either alone or in combination for 72 h. Flow cytometry, comet assay, MTT method and optical microscopy were used to assess cell proliferation, cell cycle, DNA damage, and morphological alterations. Gemcitabine exerted an inhibitory effect on T24 and 5637 cell proliferation, in a concentration-dependent manner. Everolimus significantly reduced proliferation of 5637 bladder cancer cells (IC₃₀) at 1 μM), whereas T24 demonstrated marked resistance to everolimus treatment. A significant antiproliferative effect was obtained combining gemcitabine (100 nM) with everolimus (0.05-2 μM) with an arrest of cell cycle at S phase. Furthermore, an increase in frequency of DNA damage, apoptotic bodies, and apoptotic cells was observed when T24 and 5637 cancer cells were treated simultaneously with both drugs. Data show that in vitro combination produced a more potent antiproliferative effect when compared with single drugs.
Authors:
Rosário Pinto-Leite; Regina Arantes-Rodrigues; Carlos Palmeira; Isabel Gaivão; Maria Luís Cardoso; Aura Colaço; Lúcio Santos; Paula Oliveira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of toxicology and environmental health. Part A     Volume:  75     ISSN:  1528-7394     ISO Abbreviation:  J. Toxicol. Environ. Health Part A     Publication Date:  2012  
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-10-17     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  100960995     Medline TA:  J Toxicol Environ Health A     Country:  England    
Other Details:
Languages:  eng     Pagination:  788-99     Citation Subset:  IM    
Affiliation:
Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Antimetabolites, Antineoplastic / pharmacology
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Comet Assay
DNA Damage
Deoxycytidine / analogs & derivatives*,  pharmacology
Drug Resistance, Neoplasm
Drug Synergism
Humans
Mutagens / pharmacology
Neoplasm Invasiveness
Osmolar Concentration
S Phase / drug effects
Sirolimus / analogs & derivatives*,  pharmacology
Urinary Bladder Neoplasms / drug therapy*,  pathology
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Antineoplastic Agents; 0/Mutagens; 159351-69-6/everolimus; 53123-88-9/Sirolimus; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine

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


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