|
KMID : 0379520030190030197
|
|
한국독성학회지
2003 Volume.19 No. 3 p.197 ~ p.203
|
|
|
Apicidin-Mediated Apoptosis Signaling in Human Promyelocytic Leukemia U937 Cells
|
|
Jung Eun-Hynu
Park Chan-Hee
Lim Chang-In
Lee Hwang-Hee
Song Hoon-Seob
Yeom Seong-Seob
Jung Eun-Bae
Lee Byeong-Gon
Kim Young-Hoon
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Apicidin, U937, Apoptosis
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
 
|