Induction of enantio-selective apoptosis in human leukemia HL-60 cells by (S)-erypoegin K, an isoflavone isolated from Erythrina poeppigiana
| Autor: | Rina Nagai, Satomi Saigusa, Haruka Matsuyama, Naoki Asao, Yuto Takeuchi, Tomiyasu Murata, Kiyomi Hikita, Hitoshi Tanaka, Kuniki Kato, Norio Kaneda, Yogesh S. Wagh |
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| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Cell Survival Clinical Biochemistry Eryptosis Pharmaceutical Science Genistein Apoptosis HL-60 Cells 01 natural sciences Biochemistry High-performance liquid chromatography chemistry.chemical_compound Structure-Activity Relationship Furan Drug Discovery Tumor Cells Cultured Humans Fragmentation (cell biology) Molecular Biology IC50 Cell Proliferation Erythrina Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Methylglyoxal Stereoisomerism Antineoplastic Agents Phytogenic 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Molecular Medicine Racemic mixture Drug Screening Assays Antitumor |
| Zdroj: | Bioorganicmedicinal chemistry. 28(11) |
| ISSN: | 1464-3391 |
| Popis: | Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has potent apoptosis-inducing effect on human leukemia HL-60 cells. Erypoegin K has a chiral carbon at the C-2′′ position of its furan ring and naturally occurs as a racemic mixture of (S)- and (R)-isomers. In the present study, we semi-synthesized (RS)-erypoegin K from genistein and separated the optical isomers by HPLC using a chiral column to characterize its apoptosis-inducing activity. Apoptotic cell death was assessed by analyzing caspase-3 and caspase-9 activation, nuclear fragmentation, and genomic DNA ladder formation. (S)-erypoegin K showed exclusive anti-proliferative and apoptosis-inducing activity, with an IC50 value of 90 nM, about 50% lower than that of its racemic mixture (175 nM). By contrast, no apoptosis-inducing activity was shown by the (R)-isomer. In addition, methylglyoxal accumulation in the culture medium was observed only in cells treated with (S)-erypoegin K. These results demonstrated that (S)-erypoegin K is a unique bioactive component that has potent apoptosis-inducing activity on HL-60 cells. |
| Databáze: | OpenAIRE |
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