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甘草酸诱导 HPV18 人宫颈癌 HeLa 细胞系中依赖活性氧的细胞凋亡和 G/G 期细胞周期阻滞。

Glycyrrhizin induces reactive oxygen species-dependent apoptosis and cell cycle arrest at G/G in HPV18 human cervical cancer HeLa cell line.

机构信息

Department of Biosciences, Integral University, Dasauli, Kursi Road, Lucknow, 226026, India.

Department of Biosciences, Integral University, Dasauli, Kursi Road, Lucknow, 226026, India.

出版信息

Biomed Pharmacother. 2018 Jan;97:752-764. doi: 10.1016/j.biopha.2017.10.147. Epub 2017 Nov 6.

DOI:10.1016/j.biopha.2017.10.147
PMID:29107932
Abstract

Cervical cancer is the fourth most common cancer among women worldwide and is a major cause of morbidity and mortality. High-risk Human Papilloma Virus (mostly type 16 & 18) infection is the primary risk factor for the development of cervical carcinoma. The quest for strong, safe and cost effective natural antiproliferative agents that could reduce cervical cancer have been focussed now a day. Recently, glycyrrhizin, a triterpene glycoside (saponin) from licorice (Glycyrrhiza glabra Linn.), has been shown to exhibit potent antiproliferative and anticancer properties in a few preliminary studies. However, potential of this compound in cervical cancer has not been elucidated yet. Therefore the objective of this study was to analyze the antiproliferative and apoptotic properties of glycyrrhizin in human cervical cancer HeLa cells. Our results showed that glycyrrhizin exposure significantly reduced the cell viability of HeLa cells with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed dose-related increment in ROS production induced by glycyrrhizin. Glycyrrhizin also induced apoptosis in cervical cancer cells by exerting mitochondrial depolarization. Cell cycle study showed that glycyrrhizin induced cell cycle arrest in G/G1 phase of cell cycle in a dose dependent manner. Thus, this study confirms the efficacy of glycyrrhizin in cervical cancer cells which could be an adjunct in the better prevention and management of cervical cancer worldwide.

摘要

宫颈癌是全球女性中第四常见的癌症,也是发病率和死亡率的主要原因。高危型人乳头瘤病毒(主要为 16 型和 18 型)感染是宫颈癌发展的主要危险因素。目前,人们一直在寻找强效、安全且具有成本效益的天然抗增殖剂,以降低宫颈癌的发病率。最近,甘草中的三萜糖苷(皂苷)甘草酸苷已在几项初步研究中显示出具有很强的抗增殖和抗癌特性。然而,这种化合物在宫颈癌中的潜力尚未阐明。因此,本研究旨在分析甘草酸苷对人宫颈癌 HeLa 细胞的抗增殖和促凋亡作用。我们的结果表明,甘草酸苷暴露以剂量依赖性方式显著降低了 HeLa 细胞的细胞活力,同时伴有核固缩和 DNA 片段化的增加。细胞内 ROS 生成测定表明,甘草酸苷诱导的 ROS 产生呈剂量相关性增加。甘草酸苷还通过线粒体去极化诱导宫颈癌细胞凋亡。细胞周期研究表明,甘草酸苷以剂量依赖性方式诱导细胞周期停滞在 G1 期。因此,这项研究证实了甘草酸苷在宫颈癌细胞中的功效,这可能有助于更好地预防和管理全球范围内的宫颈癌。

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