Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels
Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels
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大黄素通过靶向氯离子通道抑制鼻咽癌细胞
DOI：
10.1016/j.biopha.2017.03.088
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发表时间：
2017
影响因子：
7.5
通讯作者：
Yang Haifeng
中科院分区：
文献类型：
--
作者：
Ma Lianshun;Yang Yaping;Yin Zizhang;Liu Mei;Wang Liwei;Chen Lixin;Zhu Linyan;Yang Haifeng
大黄素是从大黄中分离出来的天然蒽醌衍生物。最近的研究表明，大黄素对不同种类的人类癌细胞系具有抗癌活性。然而，其根本机制尚未得到很好的研究。我们前期的研究表明氯离子通道是抗癌药物的重要靶点。因此，本研究的目的是探讨氯离子通道在大黄素抗癌活性中的作用。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)和流式细胞术检测低分化人鼻咽癌细胞(CNE-2Z)和正常鼻咽上皮细胞(NP69-SV40T)的增殖、细胞周期阻滞和凋亡。结果表明，大黄素对CNE-2Z细胞生长的抑制作用较NP69-SV40T细胞更显着，并诱导CNE-2Z细胞周期阻滞和细胞凋亡，但不诱导NP69-SV40T细胞细胞周期停滞和凋亡。氯离子通道阻滞剂5-硝基-2-(3-苯基丙氨基)-苯甲酸酯(NPPB)或他莫昔芬均可阻止大黄素诱导的CNE-2Z细胞凋亡。光学显微镜和原子力显微镜（AFM）表明大黄素可引起CNE-2Z细胞凋亡体积减少（AVD）和超微结构改变，并被氯离子通道阻滞剂抑制。这些数据可能是氯离子通道阻止大黄素诱导的CNE-2Z细胞凋亡的进一步证据。全细胞膜片钳研究还表明，大黄素可以激活CNE-2Z细胞中的氯离子通道，但不能激活NP69-SV40T细胞中的氯离子通道。此外，氯离子通道阻滞剂也能抑制活化的氯离子电流，表明氯离子通道可能是大黄素在CNE-2Z细胞中发挥抗肿瘤功效的潜在靶分子。
Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum. Recent studies demonstrated that emodin has anti-cancer activity in different kinds of human cancer cell lines. However, the underlying mechanism has not been very well studied. Our previous studies showed chloride channels is an important target of anti-cancer drugs. Therefore, the purpose of this research was aimed to explore the role of chloride channels involving in the anti-cancer activity of emodin. The proliferation, cell cycle arrest and apoptosis of poorly differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry. The results indicated that emodin inhibited the CNE-2Z cell growth more significantly than NP69-SV40T cells and induced cell cycle arrest and apoptosis in CNE-2Z cells but not in NP69-SV40T cells. Chloride channel blocker 5-nitro-2-(3-phenylprop ylamino)-benzoate (NPPB) or tamoxifen both can prevent the apoptosis of CNE-2Z cells induced by emodin. Optical microscope and atomic force microscope (AFM) demonstrated that emodin can induce apoptotic volume decrease (AVD) and ultrastructure changes in CNE-2Z cell and inhibited by chloride channel blocker. These data could be a further evidence of chloride channel for preventing CNE-2Z cells from apoptosis induced by emodin. Whole cell patch clamp study also demonstrated that emodin can activate chloride channel in CNE-2Z cells but not in NP69-SV40T cells. Furthermore, the activated chloride currents can also be inhibited by chloride channel blockers indicating that chloride channel may be the potential target molecular of emodin exerting its anti-tumor efficiency in CNE-2Z cells.