Abstract
Adenoviral delivery of the p53 gene is a potential therapeutic approach for the treatment of lung cancer. Furthermore, amifostine is a cytoprotective agent and recent reports have described its potentiation of chemotherapy's antitumor activity in lung cancer. Therefore, we wished to investigate the ability of amifostine both alone and in combination with p53-based therapy to induce apoptosis, and to understand the mechanisms by which this apoptosis occurs. Using p53 null and wild-type p53 human lung cancer cells and normal human bronchial epithelial cells, we evaluated the effects of amifostine on proliferation and apoptosis. We then analyzed Adp53 in combination with amifostine and performed isobologram analysis. Expression of p53, p21(WAF1), Bax, Bak, bcl-2, as well as total and phosphorylated Cdc2 in the absence and presence of olomoucine, a phosphorylated Cdc2 kinase inhibitor, was then determined. Amifostine-induced apoptosis in human lung cancer cells in a dose-dependent fashion. The combination of amifostine and Adp53 significantly enhanced, with a supra-additive effect, the inhibition of proliferation of lung cancer cells. This enhancement of apoptosis by amifostine was associated with activation of p53 and dephosphoryl...Continue Reading
References
Jan 1, 1979·International Journal of Radiation Oncology, Biology, Physics·G G Steel, M J Peckham
Apr 1, 1987·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D GloverD Guerry
Jul 7, 1995·Science·S J MartinD R Green
Feb 1, 1995·Molecular and Cellular Biology·R FotedarA Fotedar
Mar 10, 1995·Science·C B Thompson
Feb 25, 1994·Science·L ShiA H Greenberg
Jun 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J H SchillerW Berry
Sep 1, 1996·Nature Medicine·J A RothD Cai
Oct 1, 1996·Nature Medicine·S L YaoA Bedi
Nov 8, 1996·The Journal of Biological Chemistry·Y FurukawaM Kitagawa
Feb 7, 1997·Cell·A J Levine
Sep 1, 1997·The Prostate·N KyprianouJ G Rhee
Jul 4, 1998·British Journal of Cancer·N ZaffaroniR Villa
Jul 17, 1998·British Journal of Cancer·H S LiuY I Chou
Jan 29, 1999·Nature·J Pines
Mar 30, 1999·Experimental Cell Research·S L HsuS C Yin
May 18, 1999·Journal of the National Cancer Institute·S G SwisherM K Waugh
May 26, 1999·The Journal of Pathology·C Prives, P A Hall
Mar 14, 2000·Oncogene·S NorthP Hainaut
Apr 27, 2000·Leukemia Research·I RibizziP Calabresi
Jun 24, 2000·International Journal of Radiation Biology·Y KataokaD J Grdina
Jan 5, 2002·International Journal of Cancer. Journal International Du Cancer·David J GrdinaLuka Milas
Aug 2, 2002·Cell·Norman E Sharpless, Ronald A DePinho
Jan 23, 2003·The Journal of Pharmacology and Experimental Therapeutics·Efstathia GiannopoulouEvangelia Papadimitriou
Mar 6, 2003·British Journal of Cancer·E J LeeR D Christen
Aug 26, 2003·Expert Review of Anticancer Therapy·Pierre-François CartronFrançois M Vallette
Aug 5, 2004·The Journal of Gene Medicine·Alioune NdoyeFrançois Guillemin
Aug 7, 2004·Gynecologic Oncology·Judith K WolfDavid M Gershenson
Sep 1, 2004·Cellular and Molecular Life Sciences : CMLS·C AkgulS W Edwards
Citations
Aug 29, 2007·Oncogene·D GrochovaJ Smardova
Sep 7, 2013·Journal of Translational Medicine·Liying ShiHua Tang
Sep 4, 2012·Oncology Reports·Yun-Fen ZuJing Guo
Jun 4, 2013·Cancer Letters·Saurabh Wadhwa, Russell J Mumper
May 27, 2010·Journal of Cancer Research and Clinical Oncology·Wu-Hua GuoJi-Xiang Zhang
Aug 3, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·David Engelmann, Brigitte M Pützer
Oct 21, 2016·Chemical Biology & Drug Design·Feng ZhangYu-Xin Li