[6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: Drug-DNA interaction and expression of certain signal genes in HeLa cells
[6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: Drug-DNA interaction and expression of certain signal genes in HeLa cells
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DOI：
10.1016/j.ejphar.2012.08.001
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发表时间：
2012-11-05
影响因子：
5
通讯作者：
Khuda-Bukhsh, Anisur Rahman
中科院分区：
文献类型：
--
作者：
Chakraborty, Debrup;Bishayee, Kausik;Khuda-Bukhsh, Anisur Rahman
[6]-姜辣素是生姜中一种非常重要的生物活性成分，据报道具有抗高血糖、抗癌和抗氧化特性，但实现这些特性的机制在很大程度上尚不清楚。本研究的重点是细胞凋亡和自噬，抗癌活性的两个关键事件，在HeLa细胞处理[6]-姜辣素。处理后的细胞表现出几种形态学变化，包括磷脂酰丝氨酸外化，DNA降解和TUNEL阳性增加。此外，线粒体膜电位的去极化，线粒体介导的细胞凋亡的证据。[6]-姜酚处理后，caspase 3和PARP的表达增加。以小牛胸腺和细胞核DNA为靶点，圆二色谱法研究药物与DNA的相互作用，结果表明药物具有与细胞核DNA结合并引起DNA构象变化的潜力。[6]-姜辣素处理可下调癌细胞中NF k β、AKT和Bcl 2基因的过表达。另一方面，在[6]-姜酚处理的细胞中，TNF α、Bax和细胞色素c的表达水平增强。因此，总体结果表明，[6]-姜辣素具有与DNA结合并通过自噬和半胱天冬酶3介导的细胞凋亡诱导细胞死亡的潜力。(c)2012爱思唯尔有限公司版权所有。
[6]-Gingerol, a pharmacologically important bioactive component of ginger, has been reported to have anti-hyperglycemic, anti-cancer and anti-oxidative properties, but mechanisms through which these are achieved are largely unclear. The present study focuses on apoptosis and autophagy, two key events of anti-cancer activity, in HeLa cells treated with [6]-gingerol. The treated cells showed several morphological changes, including externalization of phosphatidyl serine, degradation of DNA and increase in TUNEL positivity. Furthermore, there was depolarization of mitochondrial membrane potential, providing evidence of mitochondria mediated apoptosis. The expression of caspase 3 and PARP was increased in cells exposed to [6]-gingerol. Circular dichroism study for testing drug-DNA interaction with both calf thymus and nuclear DNA as target revealed that the drug had potential to bind with the nuclear DNA and induce conformational changes of DNA. The over-expression of NFk beta, AKT and Bcl2 genes in cancer cells was down-regulated by [6]-gingerol treatment. On the other hand the expression levels of TNF alpha, Bax and cytochrome c were enhanced in [6]-gingerol treated cells. Thus, overall results suggest that [6]-gingerol has potential to bind with DNA and induce cell death by autophagy and caspase 3 mediated apoptosis. (c) 2012 Elsevier B.V. All rights reserved.