Nucleophosmin/B23-binding peptide inhibits tumor growth and up-regulates transcriptional activity of p53.
The Rev peptide that binds to nucleophosmin/B23 with the highest affinity exhibited the greatest cytotoxicity on Ras-3T3 cells and inhibited tumor growth most effectively in nude mice. The efficiency of colony formation in soft agar of Ras-3T3 cells was significantly inhibited by treatment with Rev peptide. In addition, Rev peptide could potentiate the doxorubicin-induced decrease of cellular viability in U1 bladder cancer cells and inhibition of tumor growth in nude mice. Treatment of Rev peptide increased protein expression and transcriptional activity of p53 and inhibited the nucleophosmin/B23-mediated PCNA promoter activation. Peptides having high affinity of binding to molecular targets such as nucleophosmin/B23 represent a potentially useful approach to anti-cancer biotherapeutics.
Chan
Hui Jia
HJ
Chang Gung Genomics Research Center and Department of Pharmacology, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan, ROC.
Weng
Jing Jei
JJ
Yung
Benjamin Yat Ming
BY
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015694:Gene Products, rev / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D019913:Nuclear Localization Signals / Q000008:administration & dosage*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000090243:Nucleophosmin; D010455:Peptides / Q000008:administration & dosage*; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism
D015694:Gene Products, rev; C000715570:Npm1 protein, mouse; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D010455:Peptides; C503402:Rev peptide; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin