title: TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells.
abstract: Human glyoxalase I (hGLO I) is a rate-limiting enzyme in the pathway for detoxification of apoptosis-inducible methylglyoxal (MG), which is the side product of tumor-specific aerobic glycolysis. GLO I has been reported to be overexpressed in various types of cancer cells, and has been expected as an attractive target for the development of new anticancer drugs. We previously discovered a novel inhibitor of hGLO I, named TLSC702, by our in silico screening method. Here, we show that TLSC702 inhibits the proliferation of human leukemia HL-60 cells and induces apoptosis in a dose-dependent manner. In addition, TLSC702 more significantly inhibits the proliferation of human lung cancer NCI-H522 cells, which highly express GLO I, than that of GLO I lower-expressing human lung cancer NCI-H460 cells. Furthermore, this antiproliferative effect of TLSC702 on NCI-H522 cells is in a dose- and time-dependent manner. These results suggest that TLSC702 can induce apoptosis in tumor cells by GLO I inhibition, which lead to accumulation of MG. Taken together, TLSC702 could become a unique seed compound for the generation of novel chemotherapeutic drugs targeting GLO I-dependent human tumors.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takasawa
authors.forename: Nami
authors.initials: N
authors.lastname: Shimada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Uchiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshimori
authors.forename: Sei-Ichi
authors.initials: S
authors.lastname: Tanuma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: C000613648:3-(1,3-benzothiazol-2-yl)-4-(4-methoxyphenyl)but-3-enoic acid; D000970:Antineoplastic Agents; D002087:Butyrates; D013844:Thiazoles; D007791:Lactoylglutathione Lyase