Abstract:
Escape from apoptosis is one of the main demeanor characteristics of cancer cells. Mitochondria are key players in initiating and regulating the intrinsic apoptosis pathway. Hexokinase2 (HK2) is ubiquitously expressed in several cancer cells and is essential for cell survival and death. The binding of HK2 to mitochondria promotes cell proliferation, while AKT-1 mediated pathway is crucial in this process. Peimine, a steroidal alkaloid derived from plant steroids, is screened for docking properties, ADMET properties, and drug-likeness. Apoptosis targets are predicted by network pharmacology using 47 genes associated with apoptosis. According to in silico study, peimine has the potential for dual Targeting on HK2 and AKT1. For further confirmation, peimine was subjected to Cell culture studies using MRMT-1 rat breast cancer cells. The elevated levels of cytochrome c and Caspase 9 activity indicate that the intrinsic apoptosis pathway causes cell death. The decreased glucose uptake by the MRMT-1 cells indicates that pimine inhibits glucose transport by inhibiting the membrane HK2.
摘要:
凋亡逃逸是癌细胞的主要神态特征之一。线粒体是启动和调节内在凋亡途径的关键参与者。Hexopkinase2(HK2)在几种癌细胞中普遍表达,对细胞存活和死亡至关重要。HK2与线粒体的结合促进细胞增殖,而AKT-1介导的通路在这一过程中至关重要。Peimine,一种来源于植物类固醇的甾体生物碱,筛选对接属性,ADMET属性,和药物相似。通过网络药理学使用与凋亡相关的47个基因预测凋亡靶标。根据计算机模拟研究,peimine具有双重靶向HK2和AKT1的潜力。为了进一步确认,使用MRMT-1大鼠乳腺癌细胞对peimine进行细胞培养研究。细胞色素c和Caspase9活性水平的升高表明内在凋亡途径导致细胞死亡。MRMT-1细胞对葡萄糖的摄取减少表明,亚胺通过抑制膜HK2来抑制葡萄糖转运。