An image-based, high-throughput screening assay for molecules that induce excess DNA replication in human cancer cells.

ABSTRACT: Previous studies have shown DNA re-replication can be induced in cells derived from human cancers under conditions in which it is not possible for cells derived from normal tissues. Because DNA re-replication induces cell death, this strategy could be applied to the discovery of potential anticancer therapeutics. Therefore, an imaging assay amenable to high-throughput screening was developed that measures DNA replication in excess of four genomic equivalents in the nuclei of intact cells and indexes cell proliferation. This assay was validated by screening a library of 1,280 bioactive molecules on both normal and tumor-derived cells where it proved more sensitive than current methods for detecting excess DNA replication. This screen identified known inducers of excess DNA replication, such

SUBMITTER: Zhu W 

PROVIDER: S-EPMC3060295 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature