Vitexin compound 1, a novel extraction from a Chinese herb, suppresses melanoma cell growth through DNA damage by increasing ROS levels.
Vitexin compound 1, a novel extraction from a Chinese herb, suppresses melanoma cell growth through DNA damage by increasing ROS levels.
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牡荆素化合物 1 是一种从中草药中提取的新型提取物，通过增加 ROS 水平来抑制 DNA 损伤，从而抑制黑色素瘤细胞的生长。
DOI：
10.1186/s13046-018-0897-x
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发表时间：
2018-11-06
期刊：
影响因子：
--
通讯作者：
Peng C
中科院分区：
文献类型：
--
作者：
Liu N;Wang KS;Qi M;Zhou YJ;Zeng GY;Tao J;Zhou JD;Zhang JL;Chen X;Peng C
黄荆（Vitex negundol L）是马鞭草科（Verbenaceae）植物，是一种分布广泛的芳香灌木.黄荆中含有一系列化合物，在中药中用于治疗多种疾病。皮肤黑色素瘤是最具侵袭性的恶性肿瘤之一。方法首先采用CCK-8细胞计数试剂盒和集落形成实验检测VB1（Vitexin compound 1）对黑色素瘤细胞活力的影响，然后采用流式细胞仪检测细胞凋亡和细胞周期，免疫印迹法检测细胞凋亡。在异种移植小鼠模型中评价VB 1的体内作用。通过RNA测序分析VB1抗肿瘤作用的可能机制，并通过实时荧光定量PCR验证关键差异表达基因。结果在本研究中，我们发现从中药黄荆种子中提取的化合物VB 1在体外和体内均能阻断黑色素瘤细胞的生长，使细胞周期阻滞于G2/M期，并诱导黑色素瘤细胞凋亡，而在正常细胞中未观察到显著的效果。为了研究VB1的细节，我们分析了用VB1处理黑色素瘤细胞后基因表达谱的改变。研究结果表明，VB1可以影响多种黑色素瘤细胞系中的多种途径，包括p53，凋亡和细胞周期途径。此外，我们证实，VB1恢复P53通路蛋白水平，然后我们证明，VB1显着诱导ROS的积累，导致黑色素瘤细胞系的DNA损伤。有趣的是，我们的研究结果表明，VB1也增加了活性氧水平在BRAFi（BRAF抑制剂）-抗性黑色素瘤细胞，导致DNA细胞毒性，这导致G2/M期阻滞和apoptosis. ConclusionsTaken在一起，我们的研究结果表明，牡荆素化合物1可能是一个有前途的治疗中药黑色素瘤治疗BRAFi抗性无关。
BackgroundVitex negundoL (Verbenaceae) is an aromatic shrub that is abundant in Asian countries. A series of compounds fromVitex negundohave been used in traditional Chinese medicine for the treatment of various diseases. Cutaneous melanoma is one of the most aggressive malignancies. A significant feature of melanoma is its resistance to traditional chemotherapy and radiotherapy; therefore, there is an urgent need to develop novel treatments for melanoma.MethodsWe first examined the effects of VB1 (vitexin compound 1) on cell viability by CCK-8 (cell counting kit) and Colony Formation Assay; And then, we analyzed the apoptosis and cell cycle by flow cytometry, verified apoptosis by Immunoblotting. The in vivo effect of VB1 was evaluated in xenograft mouse model. Potential mechanisms of VB1’s antitumor effects were explored by RNA sequencing and the key differential expression genes were validated by real-time quantitative PCR. Finally, the intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and the DNA damage was revealed by Immunofluorescence and Immunoblotting.ResultsIn this study, we show that VB1, which is a compound purified from the seed of the Chinese herbVitex negundo, blocks melanoma cells growth in vitro and in vivo, arrests the cell cycle in G2/M phase and induces apoptosis in melanoma cell lines, whereas the effects are not significantly observed in normal cells. To study the details of VB1, we analyzed the alteration of gene expression profiles after treatment with VB1 in melanoma cells. The findings showed that VB1 can affect various pathways, including p53, apoptosis and the cell cycle pathway, in a variety of melanoma cell lines. Furthermore, we confirmed that VB1 restored the P53 pathway protein level, and then we demonstrated that VB1 significantly induced the accumulation of ROS, which resulted in DNA damage in melanoma cell lines. Interestingly, our results showed that VB1 also increased the ROS levels in BRAFi (BRAF inhibitor)-resistant melanoma cells, leading to DNA cytotoxicity, which caused G2/M phase arrest and apoptosis.ConclusionsTaken together, our findings indicate that vitexin compound 1 might be a promising therapeutic Chinese medicine for melanoma treatment regardless of BRAFi resistance.
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DOI：
10.1126/science.1253735
发表时间：
2014-11-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lo JA;Fisher DE
通讯作者：
Fisher DE
影响因子：
8.8
作者：
Kemper K;Krijgsman O;Kong X;Cornelissen-Steijger P;Shahrabi A;Weeber F;van der Velden DL;Bleijerveld OB;Kuilman T;Kluin RJC;Sun C;Voest EE;Ju YS;Schumacher TNM;Altelaar AFM;McDermott U;Adams DJ;Blank CU;Haanen JB;Peeper DS
通讯作者：
Peeper DS
影响因子：
9
作者：
通讯作者：
--
影响因子：
8
作者：
通讯作者：
--
影响因子：
7.2
作者：
Mollereau, Bertrand;Ma, Dali
通讯作者：
Ma, Dali