| Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. | |
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MedLine Citation:
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PMID: 17052670 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bee venom (BV) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in BV-induced apoptosis are still uncharacterized in human leukemic cells. In the present study, we report that BV induces apoptosis in leukemic U937 cells through downregulation of ERK and Akt signal pathway. Furthermore, BV-induced apoptosis was accompanied by downregulation of Bcl-2, activation of caspase-3 and a subsequent poly(ADP-ribose)polymerase (PARP) cleavages. The induction of apoptosis also was accompanied by the downregulation of the inhibitor of apoptosis protein (IAP) family proteins. Caspase-3 inhibitor, z-DEVD-fmk, was significantly capable of restoring cell viability and BV-induced apoptosis through caspase-3 activation was significantly attenuated in Bcl-2-overexpressing cells. These results indicate that downregulation of Bcl-2 plays a major role in the initiation as an activator of a caspase-3 involved with BV-induced apoptosis. BV also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. PD98059 (an inhibitor of ERK) or LY294002 (an inhibitor of Akt), but not an inhibitor of p38 MAPK and JNK, significantly decreased cell viability and increased lactate dehydrogenase (LDH) release. The results indicated that key regulators in BV-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of the ERK and Akt signal pathway. |
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Authors:
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Dong-Oh Moon; Sung-Yong Park; Moon-Soo Heo; Ki-Cheon Kim; Cheol Park; Woo Shin Ko; Yung Hyun Choi; Gi-Young Kim |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-08-22 |
Journal Detail:
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Title: International immunopharmacology Volume: 6 ISSN: 1567-5769 ISO Abbreviation: Int. Immunopharmacol. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-10-20 Completed Date: 2007-01-10 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 100965259 Medline TA: Int Immunopharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1796-807 Citation Subset: IM |
Affiliation:
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Faculty of Applied Marine Science, Cheju National University, Jeju, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Bee Venoms / pharmacology* Bone Marrow Cells Caspase 3 / metabolism Cell Proliferation / drug effects* Cell Survival / drug effects Collagen Type XI / metabolism DNA Fragmentation Down-Regulation Extracellular Signal-Regulated MAP Kinases / metabolism HL-60 Cells Humans K562 Cells L-Lactate Dehydrogenase / metabolism Mice Mice, Inbred C57BL Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/Bee Venoms; 0/COL11A2 protein, human; 0/Collagen Type XI; 0/Proto-Oncogene Proteins c-bcl-2; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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