Abstract
Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the present study, we investigated the anti-cancer effects of KMU-193, 2-(4-Ethoxy-phenyl)-N-{5-[2-fluoro-4-(4-methyl- piperazine-1-carbonyl)-phenylamino]-1H-indazol-3-yl}-acetamide in a human non-small cell lung cancer cell line A549. KMU-193 strongly inhibited the proliferation of A549 cells, but it did not have anti-proliferative effect in other types of cancer cell lines. KMU-193 further induced apoptosis in association with activation of caspase-3 and cleavage of PLC-γ1. However, KMU-193 had no apoptotic effect in untransformed cells such as TMCK-1 and BEAS-2B. Interestingly, pretreatment with z-VAD-fmk, a pan-caspase inhibitor, strongly abrogated KMU- 193-induced apoptosis. KMU-193 treatment enhanced the expression levels of p53 and PUMA. Importantly, p53 siRNA transfection attenuated KMU-193-induced apoptosis. Collectively, these results for the first time demonstrate that KMU-193 has strong apoptotic effects on A549 cells and these are largely mediated through caspase-3- and p53-dependent pathways.
References
Dec 20, 1996·Cancer Letters·B DonnerstagL Träger
Dec 31, 1997·Journal of the National Cancer Institute·N AhmadH Mukhtar
Jun 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S S BaeP G Suh
Jul 21, 2001·Molecular Cell·K Nakano, K H Vousden
Jan 11, 2002·The New England Journal of Medicine·Joan H SchillerUNKNOWN Eastern Cooperative Oncology Group
Nov 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G V ScagliottiUNKNOWN Italian Lung Cancer Project
Jul 3, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frank FossellaChandra P Belani
Dec 10, 2003·Oncogene·Jordan S Fridman, Scott W Lowe
Mar 10, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·George W Sledge
Jan 23, 2008·Biochemical Society Transactions·Susan E Logue, Seamus J Martin
Mar 21, 2008·Bioorganic & Medicinal Chemistry Letters·Jinho LeeSei-Hee Lee
Aug 7, 2009·Chemotherapy·Ho Cheol ShinJong-Wook Park
Feb 17, 2010·International Immunopharmacology·Jung Hwa OhTaeg Kyu Kwon
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Zhaohui Feng
Jul 22, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Ahmedin JemalElizabeth M Ward
Jun 7, 2011·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Yaping XuShenglin Ma
Jun 16, 2012·CA: a Cancer Journal for Clinicians·Rebecca SiegelElizabeth Ward
Jul 31, 2012·Japanese Journal of Clinical Oncology·Kumiko Saika, Ryoko Machii
Aug 14, 2012·Journal of Cellular Biochemistry·Shin KimJong-Wook Park
Feb 19, 2013·Oncogene·A RufiniG Melino
Feb 17, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Chun-Ju LiuFu-Sheng Wan
Mar 7, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Dong-Ming WuChun-Ting Wang
Apr 10, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Qiong LiZhen-Grong Wang