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High-throughput assay for G2 checkpoint inhibitors and identification of the structurally novel compound
M Roberge1, R G Berlinck, L Xu
1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada. michel@otter.biochem.ubc.ca
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 gamma-irradiation, isogranulatimide selectively kills MCF-7 cells lacking p53 function.