Sanguinarine inhibits vascular endothelial growth factor release by generation of reactive oxygen species in MCF-7 human mammary adenocarcinoma cells.
Sanguinarine inhibits vascular endothelial growth factor release by generation of reactive oxygen species in MCF-7 human mammary adenocarcinoma cells.
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DOI：
10.1155/2013/517698
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发表时间：
2013
影响因子：
--
通讯作者：
Ge XY
中科院分区：
文献类型：
--
作者：
Dong XZ;Zhang M;Wang K;Liu P;Guo DH;Zheng XL;Ge XY
本文研究了抗癌化合物血根碱（SAN）对人乳腺癌细胞MCF-7血管内皮生长因子（VEGF）的抑制作用及其可能机制。我们将MCF-7暴露于SAN 24小时，然后通过使用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑（MTT）还原测定来评估细胞活力。采用双抗体定量ELISA试剂盒检测人VEGF，实时荧光定量PCR检测VEGF mRNA相对表达量，流式细胞仪检测SAN对活性氧（ROS）水平的影响。SAN可明显抑制MCF-7细胞的生长，并诱导细胞凋亡。我们发现，亚毒性浓度的SAN刺激VEGF的释放，并抑制高剂量的SAN，SAN诱发的VEGF释放是模仿低浓度的H2 O2，SAN调节的VEGF抑制伴随着增加的ROS，这些变化被取消的抗氧化剂。高浓度SAN抑制MCF-7细胞VEGF mRNA的表达，表明其在转录水平上的作用，抗氧化剂也能消除这种作用。提示SAN可能通过诱导活性氧来调节MCF-7细胞VEGF的表达和释放。
The inhibitory action and the possible mechanism of anticancer compound Sanguinarine (SAN) on vascular endothelial growth factor (VEGF) in human mammary adenocarcinoma cells MCF-7 were evaluated in this study. We exposed MCF-7 to SAN for 24 h, then cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Human VEGF was measured using a paired antibody quantitative ELISA kit, relative expression of VEGF mRNA was calculated using the real-time PCR studies, and the effect of SAN on the reactive oxygen species (ROS) level was detected by the flow cytometer. Treatment with SAN remarkably inhibited growth of MCF-7 cells and induced cell apoptosis. We found that VEGF release was stimulated by subtoxic concentrations of SAN and inhibited by high dose of SAN, SAN-evoked VEGF release was mimicked by low concentration of H2O2, and SAN-regulated VEGF inhibition was accompanied by increasing of ROS; these changes were abolished by antioxidant. High concentration of SAN inhibited VEGF mRNA expression in MCF-7 cultures, suggesting an effect at transcriptional level, and was also abolished by antioxidant. The present findings indicated that the regulation of VEGF expression and release from MCF-7 cells were possibly through reactive oxygen species evoked by SAN.
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