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.
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 NH(2)-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 microg/ml) led to more cell inhibition than equivalent doses of free Tet did (1-8 microg/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 NH(2)-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.
Li
Xiaolin
X
Department of Geriartrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Zhen
Donghui
D
Lu
Xiaowei
X
Xu
Hua'e
H
Shao
Yun
Y
Xue
Qiping
Q
Hu
Yong
Y
Liu
Baorui
B
Sun
Weihao
W
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D044182:Benzylisoquinolines / Q000008:administration & dosage*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D053758:Nanoparticles; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D017382:Reactive Oxygen Species; C009438:tetrandrine; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3