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標題: Nortriptyline induces mitochondria and death receptor-mediated apoptosis in bladder cancer cells and inhibits bladder tumor growth in vivo
作者: Yuan, Sheau-Yun
Cheng, Chen-Li
Ho, Hao-Chung
Wang, Shian-Shiang
Chiu, Kun-Yuan
Su, Chung-Kuang
Ou, Yen-Chuan
Lin, Chi-Chen
關鍵字: 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium Bromide (MTT) (PubChem CID: 64965)
Bladder cancer
DMSO (PubChem CID: 679)
Dihydroethidium (DHE) (PubChem CID:128682)
Glutathione (GSH) (PubChem CID:124886)
JC-1 (PubChem CID:5492929)
N-acetyl-L-cysteine (NAC) (PubChem CID:12035)
Propidium iodide (PubChem CID:104981)
Reactive oxygen species
Tricyclic antidepressant
Tween 20 (PubChem CID:443314)
Antidepressive Agents, Tricyclic
Antineoplastic Agents
Apoptosis Regulatory Proteins
Cell Cycle Checkpoints
Cell Line, Tumor
Cell Survival
Dose-Response Relationship, Drug
Mice, Inbred C3H
Oxidative Stress
Reactive Oxygen Species
Receptors, Death Domain
Signal Transduction
Time Factors
Tumor Burden
Urinary Bladder Neoplasms
摘要: Nortriptyline (NTP), an antidepressant, has antitumor effects on some human cancer cells, but its effect on human bladder cancer cells is not known. In this study, we used a cell viability assay to demonstrate that NTP is cytotoxic to human TCCSUP and mouse MBT-2 bladder cancer cells in a concentration and time-dependent manner. We also performed cell cycle analysis, annexin V and mitochondrial membrane potential assays, and Western blot analysis to show that NTP inhibits cell growth in these cells by inducing both mitochondria-mediated and death receptor-mediated apoptosis. Specifically, NTP increases the expression of Fas, FasL, FADD, Bax, Bak, and cleaved forms of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. In addition, NTP decreases the expression of Bcl-2, Bcl-xL, BH3 interacting domain death agonist, X-linked inhibitor of apoptosis protein, and survivin. Furthermore, NTP-induced apoptosis is associated with reactive oxygen species (ROS) production, which can be reduced by antioxidants, such as N-acetyl-L-cysteine. Finally, we showed that NTP suppresses tumor growth in mice inoculated with MBT-2 cells. Collectively, our results suggest that NTP induces both intrinsic and extrinsic apoptosis in human and mouse bladder cancer cells and that it may be a clinically useful chemotherapeutic agent for bladder cancer in humans.
Appears in Collections:生物醫學研究所



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