Identification of small molecules inducing apoptosis by cell-based assay using fission yeast deletion mutants.

Publication Type:

Journal Article

Source:

Investigational new drugs, Volume 26, Issue 4, p.299-307 (2008)

Keywords:

2008, Antineoplastic Agents, APOPTOSIS, Center-Authored Paper, Clinical Research Division, DNA repair, Drug Screening Assays, Antitumor, Flow Cytometry Core Facility, Humans, Mitosis, Mutation, PHENOTYPE, Schizosaccharomyces, Shared Resources

Abstract:

The cell-based assay using yeast deletion mutants has been recognized as an efficient analysis to discover therapeutic compounds and reveal their mode of action. In this study, S. pombe deletion mutants-based HTS screening was carried out to identify potential anti-cancer agents. The NCI chemical library of 5700 compounds was screened using kit strains, which consisted of S. pombe mutants harboring deletions in genes involved in DNA repair and mitotic control. During the screening, we identified 40 compounds conferring growth inhibition of S. pombe. Their anti-tumorigenic properties were examined by phenotypic effect on S. pombe, flow cytometry and apoptosis analysis of human cancer. Here, we report hit compounds inducing apoptosis for development of anti-cancer agents suggesting that S. pombe deletion mutants are useful in identifying potential anti-cancer agents in human cancer therapeutics.