Nujiangexathone A, a Novel Compound Derived from Garcinia nujiangensis, Induces Caspase-Dependent Apoptosis in Cervical Cancer through the ROS/JNK Pathway.
Nujiangexathone A, a Novel Compound Derived from Garcinia nujiangensis, Induces Caspase-Dependent Apoptosis in Cervical Cancer through the ROS/JNK Pathway.
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Nu Jiangexathone A 是一种从怒江藤黄中提取的新型化合物，通过 ROS/JNK 途径诱导宫颈癌中 Caspase 依赖性细胞凋亡
DOI：
10.3390/molecules21101360
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发表时间：
2016-10-12
期刊：
影响因子：
--
通讯作者：
Xu HX
中科院分区：
文献类型：
--
作者：
Zhang L;Kong SY;Zheng ZQ;Meng XX;Feng JL;Tan HS;Lao YZ;Xiao LB;Xu HX
怒江exathone A（NJXA）是一种从怒江山竹子中提取的新化合物，对多种肿瘤细胞有抑制作用。本研究首次证明了NJXA的凋亡诱导活性及其可能的机制。我们的结果表明，NJXA抑制HeLa和SiHa细胞的集落形成的剂量依赖性的方式。Annexin V-FITC/PI染色分析表明，NJXA以剂量依赖性方式强烈触发凋亡。Western blotting分析表明，NJXA通过触发一系列事件，包括Bcl-2家族蛋白水平的变化、细胞色素c释放、caspase-3激活和染色体断裂，诱导HeLa和SiHa细胞的caspase依赖性凋亡。此外，我们证明NJXA通过激活活性氧（ROS）介导的JNK信号通路诱导细胞凋亡。与这一发现一致，ROS清除剂N-乙酰基-L-半胱氨酸（NAC，10 mM）阻碍了NJXA诱导的细胞凋亡，并减弱了HeLa和SiHa细胞对NJXA的敏感性。体内实验结果进一步证实了NJXA的抑瘤作用部分是通过诱导细胞凋亡实现的。综上所述，我们的研究结果表明，NJXA通过ROS/JNK信号通路诱导HeLa和SiHa细胞凋亡，表明NJXA可能是临床治疗宫颈癌的重要候选药物。
Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our results demonstrated that NJXA inhibited colony formation by HeLa and SiHa cells in a dose-dependent manner. An Annexin V-FITC/PI staining assay showed that NJXA strongly triggered apoptosis in a dose-dependent manner. Western blotting analyses showed that NJXA induced the caspase-dependent apoptosis of HeLa and SiHa cells by triggering a series of events, including changes in the levels of Bcl-2 family proteins, cytochrome c release, caspase-3 activation, and chromosome fragmentation. Furthermore, we demonstrated that NJXA induced cell apoptosis by activating the reactive oxygen species (ROS)-mediated JNK signaling pathway. Consistent with this finding, a ROS scavenger, N-acetyl-l-cysteine (NAC, 10 mM), hindered NJXA-induced apoptosis and attenuated the sensitivity of HeLa and SiHa cells to NJXA. In vivo results further confirmed that the tumor inhibitory effect of NJXA was partially through the induction of apoptosis. Taken together, our results demonstrated that NJXA induced the apoptosis of HeLa and SiHa cells through the ROS/JNK signaling pathway, indicating that NJXA could be important candidate for the clinical treatment of cervical cancer.
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影响因子：
7.2
作者：
Simon, HU;Haj-Yehia, A;Levi-Schaffer, F
通讯作者：
Levi-Schaffer, F
影响因子：
2.9
作者：
HERTZBERG, RP;CARANFA, MJ;HECHT, SM
通讯作者：
HECHT, SM
影响因子：
1.7
作者：
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通讯作者：
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影响因子：
12.4
作者：
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影响因子：
9
作者：
通讯作者：
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