인체 혈구암세포에 대한 단선탕(丹仙湯) 추출물의 증식억제 및 세포사멸 유도에 관한 연구

Anti-proliferative and Pro-apoptic Effects of Dan-Seon-Tang in Human Leukemia Cells

  • 김성환 (동의대학교 한의과대학 한방내과학교실) ;
  • 박상은 (동의대학교 한의과대학 한방내과학교실) ;
  • 홍상훈 (동의대학교 한의과대학 한방내과학교실)
  • Kim, Seong-Hwan (Dept. of Oriental Internal Medicine, College of Oriental Medicine, Dong-Eui university) ;
  • Park, Sang-Eun (Dept. of Oriental Internal Medicine, College of Oriental Medicine, Dong-Eui university) ;
  • Hong, Sang-Hoon (Dept. of Oriental Internal Medicine, College of Oriental Medicine, Dong-Eui university)
  • 발행 : 2011.12.30

초록

Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-${\gamma}1$, ${\beta}$-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.

키워드

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