Phytochemical Inhibition of Multidrug Resistance Protein-1 as a Therapeutic Strategy for Hemangioendothelioma.
Phytochemical Inhibition of Multidrug Resistance Protein-1 as a Therapeutic Strategy for Hemangioendothelioma.
复制标题
多药耐药蛋白 1 的植物化学抑制作为血管内皮瘤的治疗策略。
DOI：
10.1089/ars.2016.6881
复制
发表时间：
2017
影响因子：
6.6
通讯作者：
Gordillo,GayleM
中科院分区：
文献类型：
--
作者：
Biswas,Ayan;Clark,EmmaC;Sen,ChandanK;Gordillo,GayleM
目的：血管瘤是婴幼儿最常见的软组织肿瘤和血管内皮细胞肿瘤。它们经常导致畸形，并可能导致死亡。目前的药物治疗具有高风险的副作用，这限制了接受治疗的儿童数量。这项工作的目的是确定标准化浆果提取物抑制内皮细胞肿瘤生长的机制，并在体内测试这些发现。结果：EOMA细胞是一个有效的模型，当注射到同基因(129P/3)小鼠的皮下时，可以产生内皮细胞肿瘤。与赋形剂对照组相比，经粉末天然浆果提取物(NBE)处理的EOMA细胞显著抑制多药耐药蛋白-1(MRP-1)的活性。这导致氧化谷胱甘肽(GSSG)的核聚集和EOMA细胞的凋亡性死亡。免疫细胞化学显示，当NBE处理的EOMA细胞被注射到小鼠体内时，它们产生了较小的肿瘤，并且与赋形剂处理的EOMA细胞相比，有更高的细胞凋亡率。对荷瘤小鼠的Kaplan-Meier生存曲线显示，与赋形剂治疗对照组相比，NBE治疗显著延长了小鼠的生存时间。创新：这是首次报道的结果表明，浆果提取物可以抑制MRP-1功能，这种功能是通过在NADPH氧化酶高度活跃的EOMA细胞的细胞核内积聚GSSG而导致肿瘤细胞凋亡而导致病理性血管生成的。结论：这些发现表明浆果提取物抑制MRP-1活性作为一种治疗干预值得考虑和进一步研究，并可能应用于其他MRP-1活性升高的癌症。氧化还原信号。26,1009-1019。
Aims:Hemangiomas are endothelial cell tumors and the most common soft tissue tumors in infants. They frequently cause deformity and can cause death. Current pharmacologic therapies have high-risk side-effect profiles, which limit the number of children who receive treatment. The objectives of this work were to identify the mechanisms through which standardized berry extracts can inhibit endothelial cell tumor growth and test these findingsin vivo.Results:EOMA cells are a validated model that generates endothelial cell tumors when injected subcutaneously into syngeneic (129P/3) mice. EOMA cells treated with a blend of powdered natural berry extracts (NBE) significantly inhibited activity of multidrug resistance protein-1 (MRP-1) compared to vehicle controls. This resulted in nuclear accumulation of oxidized glutathione (GSSG) and apoptotic EOMA cell death. When NBE-treated EOMA cells were injected into mice, they generated smaller tumors and had a higher incidence of apoptotic cell death compared to vehicle-treated EOMA cells as demonstrated by immunocytochemistry. Kaplan–Meier survival curves for tumor-bearing mice showed that NBE treatment significantly prolonged survival compared to vehicle-treated controls.Innovation:These are the first reported results to show that berry extracts can inhibit MRP-1 function that causes apoptotic tumor cell death by accumulation of GSSG in the nucleus of EOMA cells where NADPH oxidase is hyperactive and causes pathological angiogenesis.Conclusions:These findings indicate that berry extract inhibition of MRP-1 merits consideration and further investigation as a therapeutic intervention and may have application for other cancers with elevated MRP-1 activity.Antioxid. Redox Signal. 26, 1009–1019.