Nanoparticle realgar powders induce apoptosis in U937 cells through caspase MAPK and mitochondrial pathways.
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.
Wang
Xiao-Bo
XB
School of Traditional Chinese Medicines, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Gao
Hui-Yuan
HY
Hou
Bai-Ling
BL
Huang
Jian
J
Xi
Rong-Gang
RG
Wu
Li-Jun
LJ
D017209:Apoptosis / Q000187:drug effects*; D001152:Arsenicals / Q000494:pharmacology*; D020169:Caspases / Q000502:physiology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D053758:Nanoparticles; D011208:Powders; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013440:Sulfides / Q000494:pharmacology*; D020298:U937 Cells; D051028:bcl-2-Associated X Protein / Q000502:physiology
D001152:Arsenicals; D011208:Powders; D019253:Proto-Oncogene Proteins c-bcl-2; D013440:Sulfides; D051028:bcl-2-Associated X Protein; C058317:arsenic disulfide; D020169:Caspases