TY - JOUR ID - 31342 TI - Treatment with a Small Synthetic Compound, KMU-193, induces Apoptosis in A549 Human Lung Carcinoma Cells through p53 Up-Regulation JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 Y1 - 2015 PY - 2015 VL - 16 IS - 14 SP - 5883 EP - 5887 KW - KMU-193 KW - Lung cancer KW - Apoptosis KW - caspase KW - p53 DO - N2 - Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the presentstudy, we investigated the anti-cancer effects of KMU-193, 2-(4-Ethoxy-phenyl)-N-{5-[2-fluoro-4-(4-methylpiperazine-1-carbonyl)-phenylamino]-1H-indazol-3-yl}-acetamide in a human non-small cell lung cancer cell lineA549. KMU-193 strongly inhibited the proliferation of A549 cells, but it did not have anti-proliferative effect inother types of cancer cell lines. KMU-193 further induced apoptosis in association with activation of caspase-3and cleavage of PLC-γ1. However, KMU-193 had no apoptotic effect in untransformed cells such as TMCK-1and 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 timedemonstrate that KMU-193 has strong apoptotic effects on A549 cells and these are largely mediated throughcaspase-3- and p53-dependent pathways. UR - https://journal.waocp.org/article_31342.html L1 - https://journal.waocp.org/article_31342_343f8d45be41b867301648b09170229f.pdf ER -