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1.
J Nat Med ; 72(1): 260-266, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29151157

RESUMO

Erypoegin K is an isoflavone isolated from the stem bark of Erythrina poeppigiana. It contains a furan group at the A-ring of the core isoflavone structure and can inhibit the activity of glyoxalase I, an enzyme that catalyzes the detoxification of methylglyoxal (MG), a by-product of glycolysis. In the present study, we found that erypoegin K has a potent cytotoxic effect on human leukemia HL-60 cells. Its cytotoxic effect was much stronger than that of a known glyoxalase I inhibitor S-p-bromobenzylglutathione cyclopentyl diester. Conversely, erypoegin K demonstrated weak cytotoxicity toward normal human peripheral lymphocytes. The treatment of HL-60 cells with erypoegin K significantly induced caspase-3 activity, whereas the pretreatment of the cells with caspase-3 inhibitor suppressed erypoegin K-induced cell death. Furthermore, nuclear condensation and apoptotic genome DNA fragmentation were observed in erypoegin K-treated HL-60 cells. These results indicated that the observed cell death was mediated by apoptosis. In addition, the toxic compound MG was highly accumulated in the culture medium of erypoegin K-treated HL-60 cells, suggesting that cell apoptosis was triggered by extracellular MG. The present study showed that erypoegin K has a potent apoptosis-inducing effect on cancerous cell lines, such as HL-60.


Assuntos
Benzofuranos/química , Erythrina/química , Células HL-60/química , Isoflavonas/química , Leucemia/tratamento farmacológico , Apoptose , Humanos , Leucemia/patologia
2.
Nat Prod Commun ; 10(9): 1581-4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26594764

RESUMO

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.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Erythrina/química , Isoflavonas/farmacologia , Lactoilglutationa Liase/antagonistas & inibidores , Lactoilglutationa Liase/metabolismo , Antineoplásicos Fitogênicos/química , Sobrevivência Celular , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica , Células HL-60 , Humanos , Isoflavonas/química , Lactoilglutationa Liase/genética , Estrutura Molecular
3.
Anticancer Res ; 34(9): 5021-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25202086

RESUMO

BACKGROUND/AIM: Accumulating evidence shows that various types of cancers induce a specific immune response, resulting in the production of antibodies against self-components (autoantibodies). The aim of the present study was to identify antigens for autoantibodies in sera from endometrial cancer patients as novel diagnostic markers for the disease. MATERIALS AND METHODS: The reactivity of individual sera from patients was examined by 2-dimensional (2-D) immunoblotting using HeLa cell lysates as antigens to identify autoantigens. ELISA was established to quantitatively measure autoantibody titer of patients' sera. RESULTS: A mitochondrial protein, dihydrolipoamide dehydrogenase (DLD), was identified as an autoantigen specific to endometrial cancer patients. The levels of immunoglobulin (Ig)A but not IgG autoantibody to DLD were significantly increased in the sera of endometrial cancer patients. CONCLUSION: IgA autoantibody against DLD could be a novel diagnostic marker for endometrial cancer.


Assuntos
Autoanticorpos/imunologia , Di-Hidrolipoamida Desidrogenase/imunologia , Neoplasias do Endométrio/imunologia , Proteômica , Adulto , Idoso , Biomarcadores Tumorais/imunologia , Estudos de Casos e Controles , Linhagem Celular , Di-Hidrolipoamida Desidrogenase/metabolismo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Imunoglobulina A/imunologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteômica/métodos , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/metabolismo
4.
Nucleic Acids Res ; 31(24): 7175-88, 2003 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-14654693

RESUMO

The first synthesis of 5-amino-3-(2'-deoxy-beta-D-ribofuranosyl)imidazo[4,5-b]pyridin-7-one (1-deaza-2'-deoxyguanosine) is described. The compound was converted from the known AICA-deoxyriboside. The tautomeric structure of the base moiety was determined by theoretical calculation to be a hydroxyl form. Although the analog was found to be labile to acidic conditions, 1-deaza-2'-deoxyguanosine was successfully converted into a phosphoramidite derivative, which was incorporated into oligodeoxynucleotides by the standard phosphoramidite method. Thermal stabilities of oligodeoxynucleotides containing 1-deaza-2'-deoxyguanosine were investigated by thermal denaturing experiments. Also, a triphosphate analog of 1-deaza-2'-deoxyguanosine was synthesized for polymerase extension reactions. Single nucleotide insertion reactions using a template containing 1-deaza-2'-deoxyguanosine, as well as 1-deaza-2'-deoxyguanosine triphosphate, were performed using the Klenow fragment (exonuclease minus) polymerase and other polymerases. No hydrogen bonded base pairs, even a 1-deaza-2'-deoxyguanosine:cytidine base pair, were indicated by thermal denaturing studies. However, though less selective and less effective than the natural guanosine counterpart, the polymerase extension reactions suggested the formation of a base pair of 1-deaza-2'-deoxyguanosine with cytidine during the insertion reactions.


Assuntos
Desoxiguanosina/química , Desoxiguanosina/síntese química , Pareamento de Bases , Sequência de Bases , Citidina/química , DNA Polimerase I/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Ligações de Hidrogênio , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Desnaturação de Ácido Nucleico , Nucleotídeos/metabolismo , Oligodesoxirribonucleotídeos/síntese química , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/metabolismo , Moldes Genéticos , Termodinâmica
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