Enhanced cytotoxicity and activation of ROS-dependent c-Jun NH2-terminal kinase and caspase-3 by low doses of tetrandrine-loaded nanoparticles in Lovo cells - A possible Trojan strategy against cancer
Enhanced cytotoxicity and activation of ROS-dependent c-Jun NH2-terminal kinase and caspase-3 by low doses of tetrandrine-loaded nanoparticles in Lovo cells - A possible Trojan strategy against cancer
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DOI：
10.1016/j.ejpb.2010.04.016
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发表时间：
2010-08-01
影响因子：
4.9
通讯作者：
Sun, Weihao
中科院分区：
文献类型：
--
作者：
Li, Xiaolin;Zhen, Donghui;Sun, Weihao
粉防己碱（Tetrandrine，泰特）是一种双苄基异喹啉类生物碱，通过诱导细胞凋亡、活性氧（reactive oxygen species，ROS）的形成、激活依赖于ROS的c-Jun氨基末端激酶（c-Jun NH 2-terminal kinase，JNK）和caspase-3，在体内外均具有抗肿瘤作用。然而，泰特的不溶性限制了它的应用。越来越多的证据表明，开发具有改善的溶解性、稳定性和细胞毒性的亲脂性泰特的特洛伊策略的纳米级递送系统是可能的。在这里，我们首先报道了一种简单的方法来生产基于两亲性嵌段共聚物的Tet-loaded纳米粒子。体外释放实验研究了Tet-np的控释特性。细胞毒性实验证实Tet-np对Lovo细胞有抗肿瘤作用。此外，在较低浓度（1-8 μ g/ml）下的Tet-np剂量导致比等同剂量的游离泰特（1-8 μ g/ml）更多的细胞抑制。结果表明，等剂量的泰特纳米粒可诱导更高的摄取效率、更多的活性氧（ROS）产生以及更强的ROS依赖性c-Jun氨基末端激酶（JNK）和caspase-3的激活。虽然目前的结果表明，Tet-np可能是一个潜在的有用的化疗工具，深入的研究仍然是必要的。(C)2010 Elsevier BV保留所有权利。
Tetrandrine (Tet), a bis-benzylisoquinoline alkaloid, has recently been reported as a novel anti-cancer agent in vitro and in vivo by inducing apoptosis with the formation of reactive oxygen species (ROS) and the activation of ROS-dependent c-Jun NH2-terminal kinase (JNK) and caspase-3. However, application of Tet is limited for its insolubility. Accumulated evidences raise the possibility of developing nanoscale delivery systems of Trojan strategy with improved solubility, stability and cytotoxicity of lipophilic Tet. Here, we reported first a simple way to produce Tet-loaded nanoparticles based on amphiphilic block copolymer. The controlled release pattern of Tet-loaded nanoparticles (Tet-np) was characterized by in vitro release experiments. Cytotoxicity tests proved anti-tumor effect of Tet-np against Lovo cells. Moreover, doses of Tet-np during lower concentrations (1-8 mu g/ml) led to more cell inhibition than equivalent doses of free Tet did (1-8 mu g/ml). It was further presented that the higher uptake efficiency, more reactive oxygen species (ROS) generation, and the stronger activation of ROS-dependent c-Jun NH2-terminal kinase (JNK) and caspase-3 were induced by the equivalent dose of Tet delivered by nanoparticles. Although the present results suggested that Tet-np could be a potential useful chemotherapeutic tool, intensive researches are still warranted. (C) 2010 Elsevier B.V. All rights reserved.