Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun N-terminal kinase pathway
Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun N-terminal kinase pathway
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Vitexin 6 是一种新型木酚素，通过激活 Jun N 末端激酶途径诱导自噬和细胞凋亡
DOI：
10.1097/cad.0b013e328364e8d3
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发表时间：
2013-10
影响因子：
2.3
通讯作者：
Chen, Yiding
中科院分区：
文献类型：
--
作者：
Zhou, Jun;Hu, Huiyong;Long, Jingpei;Wan, Fang;Li, Lili;Zhang, Suzhan;Shi, Yuenian E.;Chen, Yiding
先前的研究已经报道了牡荆素诱导细胞毒性作用。在本研究中，我们研究了一种新的天然木脂素牡荆素6（VB 6）在体外，以确定其细胞毒性的分子机制。我们筛选并培养了几种肿瘤细胞系，随后使用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑测定法分析了VB 6对14种不同肿瘤细胞系的细胞毒性。使用蛋白质印迹分析确定调节细胞凋亡和自噬的蛋白质的表达。VB 6在体外对多种肿瘤细胞株显示出良好的细胞毒作用。它诱导癌细胞凋亡和自噬。VB 6诱导的细胞凋亡表现出时间依赖性和浓度依赖性的关系，裂解的聚（ADP-核糖）聚合酶，裂解的caspase-3，Bax上调，Bcl-2下调。Beclin-1和LC 3-II的水平是细胞自噬的标志物，在VB 6处理后逐渐增加。Jun N-末端激酶（JNK）磷酸化水平在VB 6处理后增加，同时P-Bcl-2和P-C-Jun表达上调。与JNK抑制剂共处理显著降低VB 6诱导的细胞死亡和下调P-Bcl-2，并切割PARP和Beclin-1的表达。新的天然木脂素VB 6通过激活JNK通路抑制癌细胞增殖。我们认为，VB 6可能是一个有价值的化疗药物后，进一步评估。
Previous studies have reported that vitexins induce cytotoxic effects. In the present study, we investigate a new native lignan vitexin 6 (VB6) in vitro to determine the molecular mechanism underlying its cytotoxicity. We screened and cultured several tumor cell lines and subsequently analyzed VB6 cytotoxicity against 14 different tumor cell lines using a 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The expression of proteins that regulate apoptosis and autophagy was determined using western blot analysis. VB6 showed an excellent cytotoxic effect against various cancer cell lines in vitro. It induced apoptosis and autophagy of cancer cells. VB6-induced apoptosis showed a time-dependent and concentration-dependent relationship with cleaved poly (ADP-ribose) polymerase, cleaved caspase-3, Bax upregulation, and Bcl-2 downregulation. The levels of Beclin-1 and LC3-II, which are markers for cell autophagy, gradually increased after VB6 treatment. Jun N-terminal kinase (JNK) phosphorylation was increased after VB6 treatment, accompanied by upregulation of P-Bcl-2 and P-C-Jun expression. Cotreatment with a JNK inhibitor significantly decreased VB6-induced cell death and downregulated P-Bcl-2, and cleaved PARP and Beclin-1 expression. The new native lignan VB6 inhibits cancer cell proliferation by activating the JNK pathway. We believe that VB6 could be a valuable chemotherapeutic drug after further evaluation.
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DOI：
10.1158/1078-0432.ccr-09-0661
发表时间：
2009-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Zhou Y;Liu YE;Cao J;Zeng G;Shen C;Li Y;Zhou M;Chen Y;Pu W;Potters L;Shi YE
通讯作者：
Shi YE
影响因子：
3.8
作者：
McCann SE;Thompson LU;Nie J;Dorn J;Trevisan M;Shields PG;Ambrosone CB;Edge SB;Li HF;Kasprzak C;Freudenheim JL
通讯作者：
Freudenheim JL
DOI：
--
发表时间：
2006-10
期刊：
The Indian journal of medical research
影响因子：
--
作者：
V. Tandon;Rahul Gupta
通讯作者：
V. Tandon;Rahul Gupta
DOI：
10.1093/jnci/djk096
发表时间：
2007-03
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
M. Touillaud;A. Thiébaut;A. Fournier;M. Niravong;M. Boutron‐Ruault;F. Clavel-Chapelon
通讯作者：
M. Touillaud;A. Thiébaut;A. Fournier;M. Niravong;M. Boutron‐Ruault;F. Clavel-Chapelon
影响因子：
5.7
作者：
Chen, Li-Hua;Fang, Jing;Lin, Xu
通讯作者：
Lin, Xu