Asian Pacific Journal of Cancer Prevention

  • 제16권14호
  • /
  • Pages.5883-5887
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  • 2015
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Treatment with a Small Synthetic Compound, KMU-193, induces Apoptosis in A549 Human Lung Carcinoma Cells through p53 Up-Regulation

  • Choi, Eun Young (Department of Internal Medicine, Yeungnam University College of Medicine) ;
  • Shin, Kyeong-Cheol (Department of Internal Medicine, Yeungnam University College of Medicine) ;
  • Lee, Jinho (Department of Chemistry, Keimyung University) ;
  • Kwon, Taeg Kyu (Department of Immunology, School of Medicine, Keimyung University) ;
  • Kim, Shin (Department of Immunology, School of Medicine, Keimyung University) ;
  • Park, Jong-Wook (Department of Immunology, School of Medicine, Keimyung University)
  • 발행 : 2015.09.02
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초록

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-methylpiperazine-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-${\gamma}1$. 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.

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참고문헌

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