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N-phenethyl-2-phenylacetamide isolated from Xenorhabdus nematophilus induces apoptosis through caspase activation and calpain-mediated Bax cleavage in U937 cells

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Author(s)
Seok-Young HwangSeunguk PaikSun-Ho ParkHyun-Su KimIn-Seon LeeSang-Pyo KimWon-Ki BaekMin-Ho SuhTaeg Kyu KwonJong-Wook ParkJae-Bok ParkJung-Jeung LeeSeong-Il Suh
Keimyung Author(s)
Kim, Sang PyoBaek, Won KiSuh, Min HoSuh, Seong IlKwon, Taeg KyuPark, Jong WookLee, Jung Jeung
Department
Dept. of Pathology (병리학)
Dept. of Microbiology (미생물학)
Dept. of Immunology (면역학)
Dept. of Preventive Medicine (예방의학)
Journal Title
International Journal of Oncology
Issued Date
2003
Volume
22
Issue
1
Abstract
The present study was designed to assess the mechanism of N-phenethyl-2-phenylacetamide (NPPA), one of three new compounds isolated from Xenorhabdus nematophilus, on the induction of apoptosis in U937 cells. NPPA displayed strong inhibitory effects on cell proliferation and viability of U937 cells and induced apoptosis. Investigation of the mechanism of NPPA-induced apoptosis revealed that treatment with NPPA produced morphological features of apoptosis and DNA fragmentation. This was associated with caspase-3 activation and cleavage of poly(ADP-ribose) polymerase. U937 cells treated with NPPA demonstrated cytochrome c accumulation in the cytosol during apoptosis induction. Pretreatment of cells with the pan-caspase inhibitor (z-VAD-fmk) prevented NPPA-induced apoptosis. These results suggested that NPPA induces apoptosis through cytochrome c-dependent caspase-3 activation in U937 cells. In late stage of apoptosis, 18 kDa fragment of Bax was generated with the down-regulation of the expressions of XIAP following NPPA treatment, suggesting that the modulation of Bax and XIAP proteins plays some roles in NPPA-mediated apoptosis. Pretreatments of z-VAD-fmk and the calpain inhibitor, calpeptin, inhibited Bax cleavage. Pretreatment of z-VAD-fmk restored the expression level of XIAP, but pretreatment of calpeptin did not. These results suggest that the elevated caspase activities cleave XIAP in this experiment. And Bcl-2 over-expression attenuates NPPA-induced apoptosis by inhibiting caspase-3 activation, and subsequently inhibits calpain autolysis and Bax cleavage. These results suggested that Bax cleavage is mediated by calpain, and calpain activation may be caspase-dependent. Taken together, the apoptotic effects of NPPA may be related, in part to the caspase-3 activation, the down-regulation of XIAP, and Bax cleavage mediated by caspase-dependent calpain activation.
Keimyung Author(s)(Kor)
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Publisher
School of Medicine
Citation
Seok-Young Hwang et al. (2003). N-phenethyl-2-phenylacetamide isolated from Xenorhabdus nematophilus induces apoptosis through caspase activation and calpain-mediated Bax cleavage in U937 cells. International Journal of Oncology, 22(1), 151–157. doi: 10.3892/ijo.22.1.151
Type
Article
ISSN
1019-6439
Source
https://www.spandidos-publications.com/ijo/22/1/151
DOI
10.3892/ijo.22.1.151
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35931
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
1. School of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학)
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