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

Investigational New Drugs
Kyung-Sook ChungMisun Won

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.

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Citations

Nov 12, 2013·International Journal of Cancer. Journal International Du Cancer·Kyoung-Jae WonMisun Won
Apr 28, 2010·PLoS Genetics·Mirela MatecicJeffrey S Smith
Jan 24, 2014·American Journal of Physiology. Endocrinology and Metabolism·Yun Chau LongBor Luen Tang

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis