Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects
Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects
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DOI：
10.1016/j.tiv.2013.09.021
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发表时间：
2013-12-01
影响因子：
3.2
通讯作者：
Boumendjel, Ahcene
中科院分区：
文献类型：
--
作者：
Champelovier, Pierre;Chauchet, Xavier;Boumendjel, Ahcene
查耳酮是天然存在的具有多种药理活性的化合物。查耳酮衍生自共同结构：1，3-二苯基丙烯酮。本研究旨在更好地了解查尔酮抗癌作用的机制途径，并提供证据表明，微小的结构差异可能导致重要的机制效应差异。我们选择了两个最近研究的查耳酮（A和B），并研究了他们对胶质母细胞瘤细胞系。发现查耳酮A通过激活半胱天冬酶-3、-8和-9诱导凋亡过程（I型PCD）。查耳酮A还增加了CDK 1/细胞周期蛋白B的比值，并降低了线粒体跨膜电位（A Pm）。查耳酮B诱导自噬细胞死亡过程（II型PCD），ROS相关，但独立的半胱天冬酶和蛋白质合成。两种查耳酮均增加Bax/Bcl 2比值，降低Ki 67和CD 71抗原表达。目前的研究表明，尽管查耳酮A和B的结构接近，但发现作用机制存在显着差异。（C）2013 Elsevier Ltd.保留所有权利。
Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect. We selected two recently investigated chalcones (A and B) and investigated them on glioblastoma cell lines. It was found that chalcone A induced an apoptotic process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane potential (A Pm). Chalcone B induced an autophagic cell death process (type II PCD), ROS-related but independent of both caspases and protein synthesis. Both chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen expressions. The present investigation reveals that despite the close structure of chalcones A and B, significant differences in mechanism of effect were found. (C) 2013 Elsevier Ltd. All rights reserved.