Document Detail


Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines.
MedLine Citation:
PMID:  17363928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma (RB) cell lines. METHODS: Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells by detection of caspase 3/7 activity, by enzyme-linked immunosorbent assay for nucleosome fragments, and by cellular morphological analysis. RESULTS: Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. The 50% growth inhibitory concentration (IC(50)) of this agent was 1.9 microM in Y79 cells, 1.3 microM in WERI-RB1 cells, and 0.9 microM in RBM cells. Beta-lapachone also induced proapoptotic effects in RB cells. Treatment of Y79 cells with 1.9 microM beta-lapachone (IC(50)) resulted in a peak, fourfold induction of caspase 3/7 activity at 72 h post-treatment; a peak, 5.6-fold increase in nucleosome fragments at 96 h post-treatment; and a peak, 1.7-fold increase in the frequency of apoptotic cells at 48 h post-treatment, relative to vehicle-treated controls. CONCLUSION: Beta-lapachone induced potent cytotoxic effects in RB cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of RB.
Authors:
H R Shah; R M Conway; K R Van Quill; M C Madigan; S A Howard; J Qi; V Weinberg; J M O'Brien
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-03-16
Journal Detail:
Title:  Eye (London, England)     Volume:  22     ISSN:  0950-222X     ISO Abbreviation:  Eye (Lond)     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-13     Completed Date:  2008-09-10     Revised Date:  2010-03-23    
Medline Journal Info:
Nlm Unique ID:  8703986     Medline TA:  Eye (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  454-60     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*,  genetics
Caspase 3 / biosynthesis
Caspase 7 / biosynthesis
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Enzyme Induction
Enzyme-Linked Immunosorbent Assay / methods
Humans
Naphthoquinones / pharmacology*
Retinal Neoplasms / pathology*
Retinoblastoma / pathology*
Reverse Transcriptase Inhibitors / pharmacology*
Tumor Cells, Cultured / drug effects
Grant Support
ID/Acronym/Agency:
EY02162/EY/NEI NIH HHS; EY13812/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Naphthoquinones; 0/Reverse Transcriptase Inhibitors; 4707-32-8/beta-lapachone; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7

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


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