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Biochemistry and Biophysics

High-Throughput Assay for G2 Checkpoint Inhibitors and Identification of the Structurally Novel Compound Isogranulatimide

Michel Roberge, Roberto G. S. Berlinck, Lin Xu, Hilary J. Anderson, Lynette Y. Lim, Darko Curman, Cheri M. Stringer, Stephen H. Friend, Peter Davies, Inez Vincent, Stephen J. Haggarty, Michael T. Kelly, Robert Britton, Edward Piers and Raymond J. Andersen
Michel Roberge
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Roberto G. S. Berlinck
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Lin Xu
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Hilary J. Anderson
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Lynette Y. Lim
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Darko Curman
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Cheri M. Stringer
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Stephen H. Friend
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Peter Davies
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Inez Vincent
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Stephen J. Haggarty
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Michael T. Kelly
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Robert Britton
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Edward Piers
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Raymond J. Andersen
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DOI:  Published December 1998
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Abstract

Treatment of cancer cells lacking p53 function with G2 checkpoint inhibitors sensitizes them to the toxic effects of DNA damage and has been proposed as a strategy for cancer therapy. However, few inhibitors are known, and they have been found serendipitously. We report the development of a G2 checkpoint inhibition assay that is suitable for high-throughput screening and its application to a screen of 1300 natural extracts. We present the isolation of a new G2 checkpoint inhibitor, the structurally novel compound isogranulatimide. In combination with γ-irradiation, isogranulatimide selectively kills MCF-7 cells lacking p53 function.

Footnotes

  • ↵1 Supported by the Canadian Breast Cancer Research Initiative (to M. R.), National Cancer Institute of Canada (to R. J. A.), Natural Sciences and Engineering Research Council of Canada (R. J. A.), and Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil (to R. G. S. B.).

  • ↵2 To whom requests for reprints should be addressed, at Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3. Phone: (604) 822-2304; Fax: (604) 822-5227; E-mail: michel@otter.biochem.ubc.ca.

  • Received July 1, 1998.
  • Accepted October 9, 1998.
  • ©1998 American Association for Cancer Research.
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December 1998
Volume 58, Issue 24
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High-Throughput Assay for G2 Checkpoint Inhibitors and Identification of the Structurally Novel Compound Isogranulatimide
Michel Roberge, Roberto G. S. Berlinck, Lin Xu, Hilary J. Anderson, Lynette Y. Lim, Darko Curman, Cheri M. Stringer, Stephen H. Friend, Peter Davies, Inez Vincent, Stephen J. Haggarty, Michael T. Kelly, Robert Britton, Edward Piers and Raymond J. Andersen
Cancer Res December 15 1998 (58) (24) 5701-5706;

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High-Throughput Assay for G2 Checkpoint Inhibitors and Identification of the Structurally Novel Compound Isogranulatimide
Michel Roberge, Roberto G. S. Berlinck, Lin Xu, Hilary J. Anderson, Lynette Y. Lim, Darko Curman, Cheri M. Stringer, Stephen H. Friend, Peter Davies, Inez Vincent, Stephen J. Haggarty, Michael T. Kelly, Robert Britton, Edward Piers and Raymond J. Andersen
Cancer Res December 15 1998 (58) (24) 5701-5706;
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