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Esculetin Induces Apoptosis through Caspase-3 Activation in Human Leukemia U937 Cells

Esculetin의 caspase-3 활성을 통한 U937 인체 혈구암세포의 세포사멸 유도

  • Park, Cheol (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Hyun, Sook-Kyung (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Shin, Woo-Jin (Departments of Physiology, College of Oriental Medicine, Dong-Eui University) ;
  • Chung, Kyung-Tae (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Choi, Byung-Tae (Division of Meridian and Structural Medicine, School of Oriental Medicine, Pusan National University) ;
  • Kwon, Hyun-Ju (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Hwang, Hye-Jin (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Kim, Byung-Woo (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Park, Dong-Il (Departments of Physiology, College of Oriental Medicine, Dong-Eui University) ;
  • Lee, Won-Ho (Department of Biology, College of Natural Sciences, Pusan National University) ;
  • Choi, Yung-Hyun (Blue-Bio Industry RIC, Dong-Eui University)
  • 박철 (동의대학교 블루바이오 소재개발센터) ;
  • 현숙경 (동의대학교 블루바이오 소재개발센터) ;
  • 신우진 (동의대학교 한의과대학 내과학교실) ;
  • 정경태 (동의대학교 블루바이오 소재개발센터) ;
  • 최병태 (부산대학교 한의학전문대학원 해부학교실) ;
  • 권현주 (동의대학교 블루바이오 소재개발센터) ;
  • 황혜진 (동의대학교 블루바이오 소재개발센터) ;
  • 김병우 (동의대학교 블루바이오 소재개발센터) ;
  • 박동일 (동의대학교 한의과대학 내과학교실) ;
  • 이원호 (부산대학교 자연과학대학 생물학과) ;
  • 최영현 (동의대학교 블루바이오 소재개발센터)
  • Published : 2009.02.28

Abstract

Esculetin, a coumarin compound, has been known to inhibit proliferation and induce apoptosis in several types of human cancer cells. However, the molecular mechanisms involved in esculetin-induced apoptosis are still uncharacterized in human leukemia cells. In this study, we have investigated whether esculetin exerts anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that esculetin could inhibit cell viability in a time-dependent manner, which was associated with the induction of apoptotic cell death such as increased populations of apoptotic- sub G1 phase. Apoptosis of U937 cells by esculetin was associated with an inhibition of Bcl-2/Bax binding activity, formation of tBid, down-regulation of X-linked inhibitor of apoptotic protein (XIAP) expression, and up-regulation of death receptor 4 (DR4) and FasL expression. Esculetin treatment also induced the degradation of ${\beta}$-catenin and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthermore, a caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited sub-G1 phase DNA content, morphological changes and degradation of ${\beta}$-catenin and DEE45/ICAD. These results indicated that a key regulator in esculetin-induced apoptosis was caspase-3 in human leukemia U937 cells.

Keywords

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