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垂盆草碱通过抑制核因子κB信号通路诱导B16F-10黑色素瘤细胞凋亡。

Punarnavine induces apoptosis in B16F-10 melanoma cells by inhibiting NF-kappaB signaling.

作者信息

Manu Kanjoormana Aryan, Kuttan Girija

机构信息

Department of Immunology, Amala Cancer Research Centre, Thrissur, Kerala, India.

出版信息

Asian Pac J Cancer Prev. 2009;10(6):1031-7.

Abstract

The objective of this study was to assess the effect of Punarnavine, an alkaloid isolated from Boerhaavia diffusa, on apoptosis in B16F-10 melanoma cells. Treatment of B16F-10 melanoma cells with nontoxic concentrations of Punarnvine resulted in the presence of apoptotic bodies and DNA fragmentation in a dose dependent manner. Cell cycle analysis and TUNEL assays also confirmed the observation. The apoptotic genes p53 and caspase-3 were found upregulated in Punarnavine treated cells, whereas the antiapoptotic gene Bcl-2 was downregulated. The inhibited nuclear translocation of NF-kappaBp65, NF-kappaBp50, NF-kappaB-c-Rel, c-Fos, ATF-2 and CREB-1 in Punarnavine treated B16 F-10 cells pointed to suppression of NF-kappaB signaling by Punarnavine. All these results demonstrate that Punarnavine induces apoptosis via activation of p53 induced caspase-3 mediated pro-apoptotic signaling and suppression of NF-kappaB induced Bcl-2 mediated survival signaling.

摘要

本研究的目的是评估从白花丹中分离出的生物碱白花丹碱对B16F - 10黑色素瘤细胞凋亡的影响。用无毒浓度的白花丹碱处理B16F - 10黑色素瘤细胞,结果呈现出凋亡小体和DNA片段化,且呈剂量依赖性。细胞周期分析和TUNEL检测也证实了这一观察结果。在经白花丹碱处理的细胞中,凋亡基因p53和caspase - 3被上调,而抗凋亡基因Bcl - 2被下调。在经白花丹碱处理的B16 F - 10细胞中,NF - κBp65、NF - κBp50、NF - κB - c - Rel、c - Fos、ATF - 2和CREB - 1的核转位受到抑制,这表明白花丹碱可抑制NF - κB信号传导。所有这些结果表明,白花丹碱通过激活p53诱导的caspase - 3介导的促凋亡信号传导以及抑制NF - κB诱导的Bcl - 2介导的生存信号传导来诱导细胞凋亡。

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