Apoptosis-inducing action of two products from oxidation of sesamol, an antioxidative constituent of sesame oil: A possible cytotoxicity of oxidized antioxidant

Apoptosis-inducing action of two products from oxidation of sesamol, an antioxidative constituent of sesame oil: A possible cytotoxicity of oxidized antioxidant
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DOI:
10.1016/j.tiv.2010.05.013
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发表时间:
2010-09-01
影响因子:
3.2
通讯作者:
Oyama, Yasuo
Oyama, Yasuo
中科院分区:
医学3区
文献类型:
--
作者:
Fujimoto, Aya;Shingai, Yoshimi;Oyama, Yasuo

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芝麻油中的一种抗氧化成分芝麻素的许多作用,由于其抗氧化作用,已被报道对人类健康有益。然而,我们最近分离出两种细胞毒性产物,三聚体和四聚体的芝麻素,从氧化芝麻素的测定指导纯化。在这项研究中,我们揭示了这些产品在大鼠胸腺细胞和人白血病K562细胞的细胞毒性特性。在10-30 μ M的三聚体或四聚体的细胞孵育24小时显着增加细胞的致死率和人口的大鼠胸腺细胞含有亚二倍体DNA,这表明细胞死亡与DNA片段,而不是30 μ M的sesophosphate的情况。当四聚体浓度为10-30 μ M时,其对大鼠胸腺细胞的细胞毒作用强于三聚体。用10 μ M四聚体孵育细胞24小时增加了暴露磷脂酰丝氨酸的细胞群、半胱天冬酶活性和DNA缺口。这些结果表明四聚体诱导的细胞凋亡。在K562细胞中,与10 μ M四聚体孵育72小时可显着抑制生长,但不影响致死率。然而,30 μ M的四聚体显著增加细胞致死率。可能四聚体对正常非增殖细胞(大鼠胸腺细胞)而不是增殖性癌细胞(人白血病K562细胞)发挥更大的细胞毒性作用。可能有必要考虑芝麻素的保存条件和产品对人体健康的安全性,以免芝麻素在体内氧化。(C)2010爱思唯尔有限公司版权所有。
Many effects of sesamol, an antioxidative constituent of sesame oil, have been reported for human health benefits due to its antioxidative action. However, we recently isolated two cytotoxic products, trimer and tetramer of sesamol, from oxidation of sesamol by an assay-guided purification. In this study, we have revealed some cytotoxic characteristics of these products in rat thymocytes and human leukemia K562 cells. Incubation of cells with trimer or tetramer at 10-30 mu M for 24 h significantly increased cell lethality and population of rat thymocytes containing hypodiploid DNA, suggesting cell death with DNA fragmentation, while it was not the case for 30 mu M sesamol. The cytotoxic action of tetramer was more potent than that of trimer in rat thymocytes when their concentrations were 10-30 mu M. The incubation of cells with 10 mu M tetramer for 24 h increased the population of cells with exposed phosphatidylserine, the activity of caspases, and the nick of DNA. These results indicate tetramer-induced apoptosis. In K562 cells, the incubation with tetramer at 10 mu M for 72 h significantly inhibited the growth without affecting the lethality. However, tetramer at 30 mu M significantly increased cell lethality. It is likely that tetramer exerts more cytotoxic action on normal non-proliferative cells (rat thymocytes) rather than proliferative cancer cells (human leukemia K562 cells). It may be necessary to consider the condition for preservation of sesamol and the safety of products from in vivo oxidation of sesamol for human health. (C) 2010 Elsevier Ltd. All rights reserved.