title: Inhibitory Effect of Isoflavones from Erythrina poeppigiana on the Growth of HL-60 Human Leukemia Cells through Inhibition of Glyoxalase I.
abstract: It has been reported that many malignant human tissues, including breast, colon, and lung cancers, may show an elevated expression of glyoxalase I (GLO I). GLO I catalyzes the reaction to transform hemimercaptal, a compound formed from methylglyoxal (MG) and reduced glutathione, into S-D-lactoylglutathione, which is then converted to D-lactic acid by glyoxalase II. GLO I inhibitors are expected to be useful for inhibiting tumorigenesis through the accumulation of apoptosis-inducible MG in tumor cells. Here, we investigated the anti-proliferative activity of eight kinds of isoflavone isolated from Erythrina poeppigiana against the growth of HL-60 human leukemia cells from the viewpoint of GLO I inhibition. Of the compounds tested, the diprenyl isoflavone, isolupalbigenin, was shown to exhibit the highest anti-proliferative activity against HL-60 cells. Upon the treatment of HL-60 cells with isolupalbigenin, MG was significantly accumulated in the culture medium, and the caspase 3 activity of the cell lysate was elevated in a time-dependent manner. Thus, it is suggested that isolupalbigenin inhibits the enzyme GLO I, resulting in MG accumulation in the medium, and leading to cell apoptosis. Isolupalbigenin, with two prenyl groups in its A- and B-rings, might be expected to become a potent leading compound for the development of anticancer agents.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Hikita
authors.forename: Saori
authors.initials: S
authors.lastname: Yamada
authors.forename: Rina
authors.initials: R
authors.lastname: Shibata
authors.forename: Miyako
authors.initials: M
authors.lastname: Katoh
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Murata
authors.forename: Kuniki
authors.initials: K
authors.lastname: Kato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Norio
authors.initials: N
authors.lastname: Kaneda
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004895:Erythrina / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic; D018922:HL-60 Cells; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D007529:Isoflavones; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase