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Nanoparticle realgar powders induce apoptosis in u937 cells through caspase mapk and mitochondrial pathways

Author:
Wang, Xiao-bo, Gao, Hui-yuan, Hou, Bai-ling, Huang, Jian, Xi, Rong-gang, Wu, Li-jun
Source:
Archives of pharmacal research 2007 v.30 no.5 pp. 653-658
ISSN:
0253-6269
Subject:
DNA fragmentation, apoptosis, caspase-3, caspase-8, cell growth, dose response, mitochondria, mitogen-activated protein kinase, nanoparticles, phosphorylation, powders, protein synthesis, ribose, signal transduction
Abstract:
Nanoparticle realgar powders (NRP) inhibited U937 cell growth in a time and dose-dependent manner. U937 cells treated with NRP showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-8, -9 inhibitor (z-IETD-fmk, Ac-LEHD-CHO, respectively) and caspase-3 inhibitor (z-DEVD-fmk) partially prevented NRP -induced apoptosis. Moreover, the classical substrates of caspase-3, poly-ADP ribose polymerase (PARP) was degraded after U937 cells treatment with NRP. In addition, NRP increased the ratio of Bax/Bcl-2 protein expression. Although p38 inhibitor (SB203580) and ERK inhibitor (PD98059) failed to block cell death, JNK inhibitor (SP600125) had marked inhibitory effects on NRP -induced apoptosis. Furthermore, the phosphorylation of JNK was up-regulated, suggesting that JNK was responsible for NRP -induced apoptosis in U937 cells. These results suggested that the caspase, mitochondria and MAPK signal pathways were involved in NRP-induced U937 apoptosis.
Agid:
5482888