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KMID : 0043320070300050653
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Archives of Pharmacal Research
2007 Volume.30 No. 5 p.653 ~ p.658
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Nanoparticle Realgar Powders Induce Apoptosis in U937 Cells through Caspase MAPK and Mitochondrial Pathways
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Wang Xiao-bo
Gao Hui-yuan
Hou Bai-ling
Huang Jian
Xi Rong-gang
Wu Li-jun
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Abstract
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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.
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KEYWORD
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Realgar, Apoptosis, Bcl-2/Bax, Caspase, MAPK
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