Molecular mechanisms of ZD1839-induced G1-cell cycle arrest and apoptosis in human lung adenocarcinoma A549 cells

Biochemical Pharmacology
Gee-Chen ChangChih-Yi Chen

Abstract

Epithelial growth factor receptor (EGFR) has been proposed as a target for anticancer therapy. ZD1839 (Iressa) is a quinazoline derivative that selectively inhibits the EGFR tyrosine kinase activity and is under clinical use in cancer patients. However, the molecular mechanisms involved in ZD1839-mediated anticancer effects remain largely uncharacterized. In this study, exposure of human lung adenocarcinoma A549 cells to ZD1839 caused G1 arrest, and subsequently induced apoptosis. Moreover, ZD1839 increased the protein levels of p27(KIP1) and retinoblastoma-related Rb2/p130 while decreased the expression of cyclin-dependent kinase-2 (CDK2), CDK4, CDK6 and cyclin-D1, cyclin-D3. In vitro kinase assay showed that ZD1839 decreased these CDKs expression in A549 cells, leading to significantly reduce their kinase activities. In addition, ZD1839-induced death of A549 cells with characteristics of apoptosis including apoptotic morphological changes, DNA fragmentation and enhancement of TUNEL-positive cell. These events were accompanied by a marked increase of Fas protein expression, and activation of caspase-2, -3, -8. Co-treatment of cells with Fas antagonist antibody significantly blocked ZD1839-induced apoptosis. Caspase-8 and caspa...Continue Reading

References

Jan 1, 1988·Annual Review of Biochemistry·Y Yarden, A Ullrich
Jun 1, 1995·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·E A Nigg
Jul 1, 1995·Critical Reviews in Oncology/hematology·D S SalomonN Normanno
Jan 1, 1995·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G FontaniniG Bevilacqua
May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Mar 9, 1995·Nature·D O Morgan
Aug 23, 1996·The Journal of Biological Chemistry·J N LavoieJ Pouysségur
Jun 1, 1996·Critical Reviews in Biochemistry and Molecular Biology·A SidleP A Hamel
Aug 1, 1997·Trends in Biochemical Sciences·D W Nicholson, N A Thornberry
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·M ChengM F Roussel
May 2, 1998·The EMBO Journal·C ScaffidiM E Peter
Jan 20, 1999·The Journal of Experimental Medicine·S A SusinG Kroemer
Aug 24, 1999·Pharmacology & Therapeutics·J R Woodburn
Mar 31, 2000·Experimental Cell Research·B Antonsson, J C Martinou
Dec 29, 2000·Drugs·J Baselga, S D Averbuch
Feb 15, 2001·Cell Death and Differentiation·M H Harris, C B Thompson
Oct 24, 2001·Current Opinion in Oncology·C L Arteaga, D H Johnson
Jan 5, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joan AlbanellJose Baselga
Feb 28, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N NormannoS Menard
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Yan-Nian ChenShih-Lan Hsu
Oct 23, 2002·Leukemia & Lymphoma·Wojciech KalasLeon Strzadala
Nov 15, 2002·Developmental Cell·Andreas Bergmann
Mar 20, 2003·Seminars in Oncology·Patricia M Lorusso
May 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Masahiro FukuokaJosé Baselga
May 22, 2003·Progress in Histochemistry and Cytochemistry·Yoshinori OtsukiMasa-Aki Shibata

❮ Previous
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Citations

May 25, 2010·Cancer Chemotherapy and Pharmacology·Hua ChengYi-Long Wu
Sep 10, 2005·Apoptosis : an International Journal on Programmed Cell Death·S SkvortsovH Zwierzina
Jul 12, 2011·Journal of Neuro-oncology·Cheng-Yi ChangChun-Jung Chen
Apr 3, 2010·Medical Oncology·Yu-Ying ChenZhan-Xiang Wang
Nov 10, 2009·Archives of Pharmacal Research·Dong-Oh MoonGi-Young Kim
Jan 20, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B CorkeryN O'Donovan
Jul 21, 2007·Acta Pharmacologica Sinica·Dong-oh MoonGi-young Kim
Aug 3, 2007·Molecular Cancer Therapeutics·Fumiyuki YamasakiNaoto T Ueno
Dec 3, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gregory J RielyCharles M Rudin
Apr 8, 2006·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Andrej RepickýViktor Milata
Apr 5, 2007·Cell Biochemistry and Biophysics·Willem I de BoerHari S Sharma
May 19, 2006·Expert Opinion on Biological Therapy·Sabrina OliveiraRaymond M Schiffelers
May 8, 2007·Biochemical and Biophysical Research Communications·Shinichi TamuraTohru Sugimoto
Aug 1, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Xiaohua ZhouXiao Han
Apr 1, 2008·Journal of Cellular and Molecular Medicine·Sharmila Adhikari, Madhav Bhatia
Sep 13, 2006·International Journal of Radiation Oncology, Biology, Physics·Mika FukutomeNorio Mitsuhashi
Feb 14, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Ján VojtassákTatiana Braxatorisová
Jun 7, 2005·Expert Opinion on Therapeutic Targets·Ladislav Novotny, Thomas Szekeres
Mar 23, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Malte KriegsEkkehard Dikomey
Dec 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gary K Schwartz, Manish A Shah
Mar 12, 2015·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·C LauandG M Machado-Santelli
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Guofang GuanKe Wang
Jul 7, 2011·Therapeutic Advances in Respiratory Disease·Divya TiwariJohann C Brandes
Nov 12, 2014·Reproduction : the Official Journal of the Society for the Study of Fertility·Meng-Ling LiuJia-Xiang Chen
Apr 27, 2007·Journal of Cellular Physiology·Marco RosettiRosella Silvestrini
Feb 14, 2006·International Journal of Cancer. Journal International Du Cancer·Marie P PiechockiFulvio Lonardo

❮ Previous
Next ❯

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