Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells
Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells
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DOI：
10.1016/j.bbrc.2012.07.053
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发表时间：
2012-08-17
影响因子：
3.1
通讯作者：
Constantinou, Andreas I.
中科院分区：
文献类型：
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作者：
Nicolaou, Katerina A.;Liapis, Vasilis;Constantinou, Andreas I.
靛玉红衍生物由于其抗癌和抗肿瘤转移的特性，近年来引起了人们的兴趣。本研究的目的是评估和比较两种新的溴取代衍生物6-溴靛玉红-3 '-肟（6 BIO）和7-溴靛玉红-3'-肟（7 BIO）在五种不同的乳腺癌细胞系中的抗癌特性。细胞活力测定鉴定出6 BIO和7 BIO在预防来自总共五个检查的乳腺癌细胞系的MDA-MB-231-TXSA乳腺癌细胞系的增殖方面最有效。此外，还发现这两种化合物通过不同的机制诱导细胞凋亡。6 BIO通过内在（线粒体）caspase-9途径诱导caspase依赖性程序性细胞死亡。7 BIO上调p21并促进G（2）/M细胞周期停滞，随后激活两种不同的凋亡途径：（a）涉及DR 4/DR 5上调和caspase-8激活的途径和（B）caspase非依赖性途径。总之，这项研究提供了重要的见解有关的分子途径，导致细胞周期停滞和凋亡的靛玉红衍生物，可以找到临床应用中的靶向癌症治疗。(C)2012 Elsevier Inc. All rights reserved.
Indirubin derivatives gained interest in recent years for their anticancer and antimetastatic properties. The objective of the present study was to evaluate and compare the anticancer properties of the two novel bromo-substituted derivatives 6-bromoindirubin-3'-oxime (6BIO) and 7-bromoindirubin-3'-oxime (7BIO) in five different breast cancer cell lines. Cell viability assays identified that 6BIO and 7BIO are most effective in preventing the proliferation of the MDA-MB-231-TXSA breast cancer cell line from a total of five breast cancer cell lined examined. In addition it was found that the two compounds induce apoptosis via different mechanisms. 6BIO induces caspase-dependent programmed cell death through the intrinsic (mitochondrial) caspase-9 pathway. 7BIO up-regulates p21 and promotes G(2)/M cell cycle arrest which is subsequently followed by the activation of two different apoptotic pathways: (a) a pathway that involves the upregulation of DR4/DR5 and activation of caspase-8 and (b) a caspase independent pathway. In conclusion, this study provides important insights regarding the molecular pathways leading to cell cycle arrest and apoptosis by two indirubin derivatives that can find clinical applications in targeted cancer therapeutics. (C) 2012 Elsevier Inc. All rights reserved.