May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
High-Throughput Identification of Antitumor Agents for Retinoblastoma
Author Affiliations & Notes
  • C. Antczak
    Memorial Sloan-Kettering Cancer Center, New York, New York
    Molecular Pharmacology and Chemistry Program,
  • C. Radu
    Memorial Sloan-Kettering Cancer Center, New York, New York
    Molecular Pharmacology and Chemistry Program,
  • E. Kim
    Memorial Sloan-Kettering Cancer Center, New York, New York
    Molecular Pharmacology and Chemistry Program,
  • H. Djaballah
    Memorial Sloan-Kettering Cancer Center, New York, New York
    Molecular Pharmacology and Chemistry Program,
  • D. H. Abramson
    Memorial Sloan-Kettering Cancer Center, New York, New York
    Ophthalmic Oncology Service,
  • Footnotes
    Commercial Relationships C. Antczak, None; C. Radu, None; E. Kim, None; H. Djaballah, None; D.H. Abramson, None.
  • Footnotes
    Support Supported in part by the Fund for Ophthalmic Knowledge
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 93. doi:
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    • Get Citation

      C. Antczak, C. Radu, E. Kim, H. Djaballah, D. H. Abramson; High-Throughput Identification of Antitumor Agents for Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):93.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: The purpose of this study is to identify potentially more potent chemotherapeutic agents for retinoblastoma.

Methods:: We developed an assay allowing the high-throughput screening (HTS) of large chemical libraries. The assay is performed in 1536-well microtiter plates in a total volume of 10 µL. We chose the Y79 cell line as a model of retinoblastoma compatible with the requirements of HTS. The Alamar blue assay we employed relies on the reduction of the resazurin dye by metabolically active cells. The resulting fluorescence is proportional to the number of live cells, which allows to monitor the cytotoxicity of compounds in a high-throughput fashion.

Results:: The statistical performance of the assay was asssessed in a control run and demonstrated the robustness of the miniaturized assay (Z’=0.71). The assay was validated in a pilot screen of 2,640 known bioactive chemicals. This study led to the identification of several known cytotoxic agents belonging to different pharmacological classes (including ion pump effectors, topoisomerase inhibitors and microtubule inhibitors) as potent antitumor agents for retinoblastoma cells.

Conclusions:: These results demonstrate that the newly developed assay is highly amenable to HTS. The strategy employed in this study should allow the rapid screening of our library of more than 200,000 compounds and potentially identify original antitumor agents for retinoblastoma.

Keywords: retinoblastoma • drug toxicity/drug effects • tumors 
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