Identification of small molecules inducing apoptosis by cell-based assay using fission yeast deletion mutants.
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.
Chung
Kyung-Sook
KS
Functional Genomics, KRIBB, Yusong, Daejeon 305-806, South Korea.
Yim
Nam-Hui
NH
Lee
Seung-Hee
SH
Choi
Shin-Jung
SJ
Hur
Kyung-Sun
KS
Hoe
Kwang-Lae
KL
Kim
Dong-Uk
DU
Goehle
Sondra
S
Kim
Hyung-Bae
HB
Song
Kyung-Bin
KB
Yoo
Hyang-Sook
HS
Bae
Ki-Hwan
KH
Simon
Julian
J
Won
Misun
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D009154:Mutation; D010641:Phenotype; D012568:Schizosaccharomyces / Q000235:genetics*
D000970:Antineoplastic Agents