Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Apicidin-Mediated Apoptosis Signaling in Human Promyelocytic Leukemia U937 Cells

Apicidin, Histone-Deacetylase Inhibitor에 의한 Promyelocytic U937 세포고사

  • 정은현 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터, 전남대학교 생물학과 분자세포생리학교실) ;
  • 박찬희 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터) ;
  • 임창인 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터) ;
  • 이황희 (전남대학교 생물학과 분자세포생리학교실) ;
  • 송훈섭 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터) ;
  • 염성섭 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터) ;
  • 정은배 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터) ;
  • 이병곤 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터) ;
  • 김영훈 (원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터)
  • Published : 2003.09.01
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Abstract

Apicidin, a histone-deacetylase inhibitor, has been successfully used to inhibit the growth of cancer cells. In this study, the apoptotic potential and mechanistic insights of apicidin were investigated in human myeloid leukemia U937 cells. Treatment of U937 cells with apicidin resulted in a decrease of cell viability with apoptotic characteristics, including chromatin condensation and ladder-pattern fragmentation of genomic DNA. Apicidin converted the procaspase-3 protease to catalytically active effector protease, resulting in subsequent cleavage of poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, apicidin induced the activation of caspase-9 protease and the cytosolic release of mitochondrial cytochrome c with mitochon-drial membrane potential transition. Moreover, apicidin transiently increased the expression of Fas and Fas ligand proteins. Taken together, the results suggest that apicidin induces apoptosis of U937 cells through activation of intrinsic caspase cascades and Fas/FasL system with mitochondrial dysfunction.

Keywords

References

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