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一种新型合成莪术二酮衍生物(ZPD)对人宫颈癌细胞凋亡诱导及抗迁移作用的影响。

Effects of a new synthetic zerumbone pendant derivative (ZPD) on apoptosis induction and anti-migratory effects in human cervical cancer cells.

作者信息

Saranya J, Dhanya B P, Greeshma Gopalan, Radhakrishnan K V, Priya S

机构信息

Chemical Sciences and Technology Division, CSIR - National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Trivandrum 695019, Kerala, India.

Chemical Sciences and Technology Division, CSIR - National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Trivandrum 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.

出版信息

Chem Biol Interact. 2017 Dec 25;278:32-39. doi: 10.1016/j.cbi.2017.10.006. Epub 2017 Oct 5.

Abstract

A newly synthesised zerumbone pendant derivative (ZPD) was studied in human cervical cancer cells (HeLa) for its anticancer properties. ZPD significantly inhibited the growth of human cervical cancer cells with a GI value of 6.35 ± 1.30 μM, which also induced morphological changes and apoptosis in a dose-dependent manner. Our data indicated that ZPD actively encouraged programmed cell death in HeLa cells which were confirmed by DNA fragmentation, phosphatidylserine translocation, increased activity of caspase 3, upregulation of the expression of the pro-apoptotic protein Bax, cleaved PARP, cleaved caspase 3 and downregulation of anti-apoptotic protein Bcl-2. ZPD also inhibited cell migration of HeLa cells, decreasing the production of MMP-2,-9 and downregulation of expression of MMPs and pro-angiogenic factor VEGF. Also it is nontoxic to normal rat cardiac myoblasts. Overall, ZPD is a promising candidate for inducing cytotoxicity, apoptosis and anti-migratory effects in cervical cancer cells.

摘要

一种新合成的零陵香酮衍生物(ZPD)在人宫颈癌细胞(HeLa)中进行了抗癌特性研究。ZPD显著抑制人宫颈癌细胞的生长,其GI值为6.35±1.30μM,还以剂量依赖性方式诱导细胞形态变化和凋亡。我们的数据表明,ZPD积极促进HeLa细胞的程序性细胞死亡,这通过DNA片段化、磷脂酰丝氨酸易位、半胱天冬酶3活性增加、促凋亡蛋白Bax表达上调、PARP裂解、半胱天冬酶3裂解以及抗凋亡蛋白Bcl-2表达下调得以证实。ZPD还抑制HeLa细胞的迁移,减少MMP-2、-9的产生,并下调MMPs和促血管生成因子VEGF的表达。此外,它对正常大鼠心肌成肌细胞无毒。总体而言,ZPD是诱导宫颈癌细胞细胞毒性、凋亡和抗迁移作用的有前景的候选物。

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