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新橙皮苷通过激活Bcl-2/Bax介导的信号通路诱导人乳腺癌MDA-MB-231细胞凋亡。

Neohesperidin induces cellular apoptosis in human breast adenocarcinoma MDA-MB-231 cells via activating the Bcl-2/Bax-mediated signaling pathway.

作者信息

Xu Fei, Zang Jia, Chen Daozhen, Zhang Ting, Zhan Huiying, Lu Mudan, Zhuge Hongxiang

机构信息

Department of Laboratory Medicine, Wuxi Municipal Women and Children Health Hospital, Wuxi 214002, Jiangsu Province, China.

出版信息

Nat Prod Commun. 2012 Nov;7(11):1475-8.

Abstract

Neohesperidin, a flavonoid compound found in high amounts in Poncirus trifoliata, has free radical scavenging activity. For the first time, our study indicated that neohesperidin also induces cell apoptosis in human breast adenocarcinoma MDA-MB-231 cells, which was possibly mediated by regulating the P53/Bcl-2/Bax pathway. MDA-MB-231 cells were subjected to treatment with neohesperidin. MTT and Trypan blue exclusion assays were applied to assess the cell viability. The morphological changes of cells were observed using an inverted microscope, and cell apoptosis was detected by flow cytometric analysis. Immunoblot analysis was conducted to evaluate the protein expressions of apoptosis-related genes, including P53, Bcl-2 and Bax. Our results indicated that the proliferation of MDA-MB-231 cells was inhibited by the treatment with neohesperidin in a time- and dose-dependent manner. The IC50 values of neohesperidin at 24 and 48 h were 47.4 +/- 2.6 microM and 32.5 +/- 1.8 microM, respectively. The expressions of P53 and Bax in the neohesperidin-treated cells were significantly up-regulated, while that of Bcl-2 was down-regulated. Our study suggested that neohesperidin could induce apoptosis of MDA-MB-231 cells, a process which was associated with the activation of the Bcl-2/Bax-mediated signaling pathway.

摘要

新橙皮苷是一种在枳壳中大量存在的黄酮类化合物,具有自由基清除活性。我们的研究首次表明,新橙皮苷还可诱导人乳腺腺癌MDA-MB-231细胞凋亡,这可能是通过调节P53/Bcl-2/Bax通路介导的。用新橙皮苷处理MDA-MB-231细胞。采用MTT法和台盼蓝排斥试验评估细胞活力。使用倒置显微镜观察细胞的形态变化,并通过流式细胞术分析检测细胞凋亡。进行免疫印迹分析以评估凋亡相关基因(包括P53、Bcl-2和Bax)的蛋白表达。我们的结果表明,新橙皮苷处理以时间和剂量依赖性方式抑制MDA-MB-231细胞的增殖。新橙皮苷在24小时和48小时的IC50值分别为47.4±2.6微摩尔和32.5±1.8微摩尔。新橙皮苷处理的细胞中P53和Bax的表达显著上调,而Bcl-2的表达下调。我们的研究表明,新橙皮苷可诱导MDA-MB-231细胞凋亡,这一过程与Bcl-2/Bax介导的信号通路激活有关。

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