Safranal, a Crocus sativus L constituent suppresses the growth of K-562 cells of chronic myelogenous leukemia. In silico and in vitro study
Safranal, a Crocus sativus L constituent suppresses the growth of K-562 cells of chronic myelogenous leukemia. In silico and in vitro study
复制标题
DOI：
10.1016/j.fct.2014.09.001
复制
发表时间：
2014-12-01
影响因子：
4.3
通讯作者：
Sinakos, Zacharias
中科院分区：
文献类型：
--
作者：
Geromichalos, George D.;Papadopoulos, Theophanis;Sinakos, Zacharias
藏红花素是番红花（藏红花）的主要成分，已被发现可抑制表达 Bcr-Abl 蛋白酪氨酸激酶活性的 K-562 人慢性粒细胞白血病 (CML) 细胞的生长。我们研究的目的是通过计算机模拟方法研究生物活性藏红花成分藏红花素 (CRC) 和番红花醛 (SFR) 抑制 Bcr-Abl 蛋白活性的能力，以及这些化合物对 K-562 生长和 Bcr-Abl 基因表达的体外影响。二氧化硅分子对接研究表明，大多数 SFR 可以附着在 Bcr-Abl 蛋白上，位于该蛋白的结合腔内，与用于治疗 CML 的药物甲磺酸伊马替尼 (IM) 位于同一位置。预测的极性相互作用和疏水接触在活性位点内构建疏水空腔，解释了观察到的抑制活性。细胞毒性实验表明SFR和CRC介导对K562细胞的细胞毒性反应。 Bcr-Abl 基因表达的体外研究表明，SFR 和 IM 在较小程度上抑制了该基因的表达，而相比之下，CRC 则诱导了该基因的表达增加。最终目标是评估藏红花成分 SFR 和 CRC 是否存在潜在的抗肿瘤活性。 (C) 2014 Elsevier Ltd. 保留所有权利。
Crocin, a main constituent of Crocus sativus L (saffron), has been found to inhibit the growth of K-562 human chronic myelogenous leukemia (CML) cells expressing Bcr-Abl protein tyrosine kinase activity. The aim of our study is to investigate the ability of the bioactive saffron's constituents, crocin (CRC) and safranal (SFR), to inhibit the Bcr-Abl protein activity employing an in silico approach, as well as the in vitro effect of these compounds on K-562 growth and gene expression of Bcr-Abl. In silica molecular docking studies revealed that mostly SFR can be attached to Bcr-Abl protein, positioned inside the protein's binding cavity at the same place with the drug used in the treatment of CML, imatinib mesylate (IM). The predicted polar interactions and hydrophobic contacts constructing a hydrophobic cavity inside the active site, explain the observed inhibitory activity. Cytotoxicity experiments showed that SFR and CRC mediate cytotoxic response to K562 cells. In vitro studies on the expression of Bcr-Abl gene revealed that SFR and in a lesser degree IM inhibited the expression of the gene, while in contrast CRC induced an increase. The ultimate goal was to evaluate the existence of a potential antitumor activity of saffron's constituents SFR and CRC. (C) 2014 Elsevier Ltd. All rights reserved.