中山大学:烟酰胺诱导宫颈癌细胞(HeLa细胞)自杀

 

Nicotinamide induces mitochondrial-mediated apoptosis through oxidative stress in human cervical cancer HeLa cells

 

目标

 

烟酰胺参与能量代谢并影响细胞氧化还原状态并调节与细胞存活和死亡相关的多种途径。最近的研究表明它在许多癌细胞中诱导增殖抑制和凋亡。然而,关于烟酰胺对人宫颈癌细胞的影响知之甚少。我们旨在评估指定浓度的烟酰胺对HeLa细胞中细胞增殖、凋亡和氧化还原相关参数的影响,并研究其凋亡机制。

 

材料和方法

 

在处理指定浓度的烟酰胺后,通过CCK-8测定评估HeLa细胞增殖,并使用2'7'-二氯荧光素二乙酸酯测量ROS(活性氧物质)的产生。通过荧光显微镜观察细胞和核形态,证实凋亡效应,并用Annexin-V法通过流式细胞术测定HeLa细胞凋亡的凋亡率。此外,我们通过JC-1方法检测线粒体膜电位,并使用qRT-PCR和免疫印迹测量凋亡相关基因的表达。

 

主要发现

 

烟酰胺抑制HeLa细胞增殖,并在相对高浓度下显着增加ROS的积累和GSH的消耗。此外,烟酰胺通过内在的线粒体凋亡途径促进HeLa细胞凋亡。

 

意义

 

我们的研究表明,烟酰胺通过氧化应激和HeLa细胞内在的线粒体凋亡途径诱导细胞凋亡。结果表明,烟酰胺可能是一种廉价,安全和有前景的治疗剂或宫颈癌患者的新辅助化疗,对于寻找宫颈癌治疗的新药也很有用。

 

 

Aims

 

Nicotinamide participates in energy metabolism and influences cellular redox status and modulates multiple pathways related with both cellular survival and death. Recent studies have shown that it induced proliferation inhibition and apoptosis in many cancer cells. However, little is known about the effects of nicotinamide on human cervical cancer cells. We aimed to evaluate the effects of the indicated concentrations nicotinamide on cell proliferation, apoptosis and redox-related parameters in HeLa cells and investigated the apoptotic mechanism.

 

Materials and methods

 

After the treatment of the indicated concentrations nicotinamide, HeLa cell proliferation was evaluated by the CCK-8 assay and the production of ROS (reactive oxygen species) was measured using 2′,7′-Dichlorofluorescin diacetate. The apoptotic effect was confirmed by observing the cellular and nuclear morphologies with fluorescence microscope and apoptotic rate of HeLa cell apoptosis was measured by flow cytometry using Annexin-V method. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured the expression of apoptosis related genes using qRT-PCR and immunoblotting.

 

Key findings

 

Nicotinamide restrained the HeLa cell proliferation and significantly increased the accumulation of ROS and depletion of GSH at relatively high concentrations. Furthermore, nicotinamide promoted HeLa cell apoptosis via the intrinsic mitochondrial apoptotic pathway.

 

Significance

 

Our study revealed that nicotinamide induced the apoptosis through oxidative stress and intrinsic mitochondrial apoptotic pathways in HeLa cell. The results emerge that nicotinamide may be an inexpensive, safe and promising therapeutic agent or a neoadjuvant chemotherapy for cervical cancer patients, as well useful to find new drugs for cervical cancer therapy.

 

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Keywords

NicotinamideOxidative stressMitochondrial apoptotic pathwayCervical cancer

 

 

Life Sciences

Volume 181, 15 July 2017, Pages 62-69

 

Author links open overlay panelYiFengYonghuaWangChengruiJiangZishuiFangZhiqiangZhangXiaoyingLinLiweiSunWeiyingJiang

 

https://doi.org/10.1016/j.lfs.2017.06.003Get rights and content

 

 

Nicotinamide induces mitochondrial-mediated apoptosis through oxidative stress in human cervical cancer HeLa cells - ScienceDirect  https://www.sciencedirect.com/science/article/abs/pii/S0024320517302771