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首页> 外文期刊>Life sciences >Selective cytotoxicity of withaphysalins in myeloid leukemia cell lines versus peripheral blood mononuclear cells.
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Selective cytotoxicity of withaphysalins in myeloid leukemia cell lines versus peripheral blood mononuclear cells.

机译：相对于外周血单核细胞而言，枯草菌素在髓样白血病细胞系中的选择性细胞毒性。

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摘要

Withaphysalins are C(28)-steroidal lactones structurally based on the ergostane skeleton that possess antiproliferative activity against tumor cell lines. In the present study, the antileukemic actvity of withaphysalin O (1), M (2), and N (3) isolated from Acnistus arborescens, against two leukemic cell lines, HL-60 and K562, was evaluated, and the cytotoxicity compared with the effects on peripheral blood mononuclear cells (PBMC). All tested compounds reduced the number of viable cells of the tumor cell lines after 24 h of exposure, except for compound 2 against the K562 cell line. The reduction was time-and concentration-dependent, and the IC(50) values ranged from 0.7 to 3.5 microM after 72 h of incubation. In addition to the growth inhibitory properties, the drugs decreased DNA synthesis after 24 h of drug exposure evaluated by the 5-bromo-2 -deoxyuridine incorporation method. None of the tested compounds reduced the number of PBMC (IC(50)>20 microM) after 72 h of incubation, in contrast to doxorubicin that decreased viable cells and increased non-viable cells even after 24 h of incubation. Morphological analysis of treated cells using hematoxylin/eosin staining indicated the presence of necrotic cells for all tested compounds in HL-60, confirmed by the use of acridine orange/ethidium bromide staining. In addition to necrotic cells, K562 cells showed morphological alterations consistent with apoptosis.
机译：Withaphysalins是结构上基于麦角甾烷骨架的C（28）-类固醇内酯，对肿瘤细胞系具有抗增殖活性。在本研究中，评估了从侧柏（Acnistus arborescens）分离得到的紫a碱O（1），M（2）和N（3）对两种白血病细胞系HL-60和K562的抗白血病活性，并将其细胞毒性与对外周血单个核细胞（PBMC）的影响。暴露24小时后，除K2细胞系的化合物2外，所有测试的化合物均减少了肿瘤细胞系的活细胞数量。减少是时间和浓度依赖性的，孵育72小时后IC（50）值在0.7到3.5 microM之间。除具有生长抑制特性外，药物通过5-溴-2-脱氧尿苷掺入法评估暴露24小时后，DNA合成下降。与阿霉素相比，即使在孵育24小时后，阿霉素也减少了存活细胞并增加了非存活细胞，但没有一种化合物能在孵育72小时后降低PBMC的数量（IC（50）> 20 microM）。使用苏木精/曙红染色对处理过的细胞进行形态学分析表明，HL-60中所有受测化合物均存在坏死细胞，这通过使用the啶橙/溴化乙锭染色证实。除坏死细胞外，K562细胞还表现出与凋亡一致的形态学改变。

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