Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells
| Autor: | Norio Kaneda, Rina Shibata, Saori Yamada, Yuko Yamakage, Tomiyasu Murata, Hitoshi Tanaka, Aya Takeda, Kuniki Kato, Natsuki Hattori, Kiyomi Hikita |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Apoptosis HL-60 Cells 03 medical and health sciences Lactoylglutathione lyase chemistry.chemical_compound 0302 clinical medicine Cytotoxic T cell Humans Cytotoxicity Benzofurans Erythrina Leukemia biology Methylglyoxal Molecular biology Isoflavones 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer cell biology.protein Molecular Medicine DNA fragmentation |
| Zdroj: | Journal of natural medicines. 72(1) |
| ISSN: | 1861-0293 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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