Abstract
p53 (N15)-Ant 32-peptide has been considered a novel and effective peptide for cancer therapy. To further enhance its anticancer effect and overcome the limitation of peptide therapy, a recombinant lentivirus was constructed in this study with the following strategies: the secretory expression of therapeutic peptide and lentivirus gene transfer system. The results demonstrated that LV-NT4(Si)-p53 (N15)-Ant could significantly suppress cell growth and induce rapid cell death in MCF-7 (overexpressed wild-type p53), HepG2 (wide-type p53), OVCAR-3 (mutant type p53) and H1299 (null p53) cells in time-dependent manners through successful gene transfer and secretory expression of therapeutic peptide at 48 h post-infection. Transmission electron microscopy and flow cytometric analysis revealed that LV-NT4(Si)-p53 (N15)-Ant could induce two different kinds of cell death (necrosis and apoptosis) by two different mechanisms, since p53 (N15)-Ant peptide has the potential of blocking interaction of mdm-2 with other protein target, and on the other hand, it could form S-shape helix-loop-helix structures, which is able to rapidly disrupt cancer cell membranes. Based on these finding, LV-NT4 (Si)-p53 (N15)-Ant may be a novel recombinant virus ...Continue Reading
References
Apr 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·N Y IpS P Squinto
Jun 1, 1993·The European Journal of Neuroscience·T TimmuskH Persson
Apr 12, 1996·Science·L NaldiniD Trono
May 15, 1997·Nature·Y HauptM Oren
May 15, 1997·Nature·M H KubbutatK H Vousden
Nov 5, 1997·Nature Biotechnology·R ZuffereyD Trono
Oct 10, 1998·Journal of Virology·T DullL Naldini
Mar 18, 2000·The Journal of Biological Chemistry·S FangA M Weissman
Mar 21, 2000·Oncogene·R Honda, H Yasuda
Sep 12, 2000·Nature Cell Biology·S D BoydT Jacks
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·M KanovskyM R Pincus
Dec 19, 2001·British Journal of Cancer·E Bálint E, K H Vousden
Mar 12, 2003·Oncogene·Tamara N DoPaul W Brandt-Rauf
Mar 26, 2003·Biochemical Society Transactions·S Laín
Apr 2, 2003·Neuroscience Letters·Desmond J SmithXin Liu
May 22, 2004·Journal of Biomedical Science·Andrew M L LeverJing Zhao
Feb 22, 2005·Advanced Drug Delivery Reviews·Ramon RosalRobert L Fine
Citations
Dec 9, 2009·Cancer Investigation·Tang XiaojiangWang Quanying
Jan 25, 2011·Cancer Science·Shi-Wen GuoWen-Zhi Li
Dec 18, 2012·Oncology Reports·Hongmin CheGuodong Gao
Nov 21, 2013·International Journal of Molecular Medicine·Lijun SunXuexin Zhang