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Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells

机译:桔皮素通过胶质瘤细胞中PTEN表达的上调诱导细胞周期停滞和凋亡

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摘要

Tangeretin (TANG), present in peel of citrus fruits, has been shown to various medicinal properties such as chemopreventive and neuroprotective. However, the chemopreventive effect of TANG on glioblastoma cells has not been examined. The present study was designed to explore the anticancer potential of TANG in glioblastoma cells and to investigate the related mechanism. Human glioblastoma U-87MG and LN-18 cells were treated with 45 mu M concentration of TANG and cell growth was measured by MTT assay. The cell cycle distribution and cell death were measured by flow cytometry. The expression of cell cycle and apoptosis related genes were analyzed by quantitative RT-PCR and western blot. The cells treated with TANG were significantly increased cell growth suppression and cell death effects than vehicle treated cells. Further, TANG treatment increases G(2)/M arrest and apoptosis by modulating PTEN and cell-cycle regulated genes such as cyclin-D and cdc-2 mRNA and protein expressions. Moreover, the ability of TANG to decrease cell growth and to induce cell death was compromised when PTEN was knockdown by siRNA. Taken together, the chemopreventive effect of TANG is associated with regulation of cell-cycle and apoptosis in glioblastoma, thereby attenuating glioblastoma cell growth. Hence, the present findings suggest that TANG may be a therapeutic agent for glioblastoma treatment. (C) 2016 Elsevier Masson SAS. All rights reserved.
机译:橘皮中存在的橘皮(TANG)已被证明具有多种医学特性,例如化学预防和神经保护作用。但是,尚未检查过TANG对胶质母细胞瘤细胞的化学预防作用。本研究旨在探讨TANG在胶质母细胞瘤细胞中的抗癌潜力,并研究其相关机制。用45μM浓度的TANG处理人胶质母细胞瘤U-87MG和LN-18细胞,并通过MTT测定法测量细胞生长。通过流式细胞术测量细胞周期分布和细胞死亡。通过定量RT-PCR和western blot分析细胞周期和凋亡相关基因的表达。与媒介物处理的细胞相比,用TANG处理的细胞具有显着增加的细胞生长抑制和细胞死亡作用。此外,TANG处理通过调节PTEN和细胞周期调控基因(如cyclin-D和cdc-2 mRNA和蛋白质表达)来增加G(2)/ M阻滞和凋亡。此外,当PTEN被siRNA敲低时,TANG减少细胞生长和诱导细胞死亡的能力受到损害。总而言之,TANG的化学预防作用与胶质母细胞瘤中细胞周期的调节和凋亡相关,从而减弱了胶质母细胞瘤细胞的生长。因此,目前的发现表明,TANG可能是胶质母细胞瘤治疗的治疗剂。 (C)2016 Elsevier Masson SAS。版权所有。

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