| Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines. | |
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MedLine Citation:
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PMID: 17363928 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-03-16 |
Journal Detail:
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Title: Eye (London, England) Volume: 22 ISSN: 0950-222X ISO Abbreviation: Eye (Lond) Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-03-13 Completed Date: 2008-09-10 Revised Date: 2010-03-23 |
Medline Journal Info:
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Nlm Unique ID: 8703986 Medline TA: Eye (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 454-60 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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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:
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EY02162/EY/NEI NIH HHS; EY13812/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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