Document Detail


In vitro radiosensitisation by trabectedin in human cancer cell lines.
MedLine Citation:
PMID:  18501589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To examine the potential radiosensitising properties of trabectedin (ET-743, Yondelis). METHODS AND MATERIALS: In vitro chemosensitivity was assessed in four tumour cell lines (DU145, HeLa, HT29, HOP62) by the crystal violet method. IC10s and IC50s were established for 1-h, 24-h and 7-day (continuous) exposure times. Radiosensitisation was evaluated by conventional colony assay. BrdUrd DNA-labelling and flow cytometry were used to analyse cell cycle kinetics. The rate of apoptotic induction was assed by annexyn-V labelling. RESULTS: Mean IC50s were 18.8 nM (10.5 - 30), 2.5 nM (1.5 - 5) and 0.25 nM (0.2-0.8) for 1 h, 24 h and continuous exposure times, respectively. HT29 and HOP62 were the most sensitive cells lines to trabectedin. Radiosensitisation was observed in DU145 and HeLa cells with a dose enhancement factor (DEF) of 1.92 and 1.77 at IC50 dose level, respectively. Trabectedin induced early S phase arrest in all cell lines studied. CONCLUSIONS: Trabectedin, at pharmacologically appropriated concentrations, harbours a significant in vitro radiosensitising effect and induces cell cycle changes and apoptosis in several human cancer cell lines. Further studies to define the clinical potential of the combination of trabectedin and radiotherapy are needed.
Authors:
Jesús Romero; Irma Zapata; Sofía Córdoba; José María Jimeno; José Antonio López-Martín; Juan Carlos Tercero; Alejandro De La Torre; Juan Antonio Vargas; Rafael Molerón; Ricardo Sánchez-Prieto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-22
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  44     ISSN:  1879-0852     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-07     Completed Date:  2008-10-13     Revised Date:  2008-11-29    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  1726-33     Citation Subset:  IM    
Affiliation:
Department of Radiation Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain. jromero.hpth@salud.madrid.org
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Alkylating / pharmacology*
Apoptosis / drug effects,  radiation effects
DNA Repair / radiation effects
Dioxoles / pharmacokinetics,  pharmacology*
Flow Cytometry
HT29 Cells / drug effects,  radiation effects
Hela Cells / drug effects,  radiation effects
Humans
Neoplasms / radiotherapy*
Radiation-Sensitizing Agents / pharmacokinetics,  pharmacology*
Tetrahydroisoquinolines / pharmacokinetics,  pharmacology*
Tumor Cells, Cultured / drug effects
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Alkylating; 0/Dioxoles; 0/Radiation-Sensitizing Agents; 0/Tetrahydroisoquinolines; 114899-77-3/trabectedin

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