| 저자(한글) |
정은현,박찬희,임창인,이황희,송훈섭,염성섭,정은배,이병곤,김영훈,원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터, 전남대학교 생물학과 분자세포생리학교실,원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터,원광대학교 의과대학 미생물학 교실 및 전정와우기관 연구센터,전남대학교 생물학과 분자세포생리학교실,원광대학교 의과대학 미생물학 교실 및 전 |
| 초록 |
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. |
