| Bcl-2 and caspase-3 are major regulators in Agaricus blazei-induced human leukemic U937 cell apoptosis through dephoshorylation of Akt. | |
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MedLine Citation:
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PMID: 17666799 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Agaricus blazei is a medicinal mushroom that possesses antimetastatic, antitumor, antimutagenic, and immunostimulating effects. However, the molecular mechanisms involved in A. blazei-mediated apoptosis remain unclear. In the present study, to elucidate the role of the Bcl-2 in A. blazei-mediated apoptosis, U937 cells were transfected with either empty vector (U937/vec) or vector containing cDNA encoding full-length Bcl-2 (U937/Bcl-2). As compared with U937/vec, U937/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2. Treatment of U937/vec with 1.0-4.0 mg/ml of A. blazei extract (ABE) for 24 h resulted in a significant induction of morphologic features indicative of apoptosis. In contrast, U937/Bcl-2 exposed to the same ABE treatment only exhibited a slight induction of apoptotic features. ABE-induced apoptosis was accompanied by downregulation of antiapoptotic proteins such as X-linked inhibitor of apoptosis protein (XIAP), inhibitor of apoptosis protein (cIAP)-2 and Bcl-2, activation of caspase-3, and cleavage of poly(ADP-ribose)polymerase (PARP). Ectopic expression of Bcl-2 was associated with significantly induced expression of antiapoptotic proteins, such as cIAP-2 and Bcl-2, but not XIAP. Ectopic expression of Bcl-2 also reduced caspase-3 activation and PARP cleavage in ABE treated U937 cells. Furthermore, treatment with the caspase-3 inhibitor z-DEVD-fmk was sufficient to restore cell viability following ABE treatment. This increase in viability was ascribed to downregulation of caspase-3 and blockage of PARP and PLC-gamma cleavage. ABE also triggered the downregulation of Akt, and combined treatment with LY294002 (an inhibitor of Akt) significantly decreased cell viability. The results indicated that major regulators of ABE-induced apoptosis in human leukemic U937 cells are Bcl-2 and caspase-3, which are associated with dephosphorylation of the Akt signal pathway. |
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Authors:
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Cheng-Yun Jin; Dong-Oh Moon; Yung Hyun Choi; Jae-Dong Lee; Gi-Young Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biological & pharmaceutical bulletin Volume: 30 ISSN: 0918-6158 ISO Abbreviation: Biol. Pharm. Bull. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-08-01 Completed Date: 2007-09-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9311984 Medline TA: Biol Pharm Bull Country: Japan |
Other Details:
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Languages: eng Pagination: 1432-7 Citation Subset: IM |
Affiliation:
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Department of Microbiology, College of Natural Sciences, Pusan National University, Busan 614-052, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Agaricus
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chemistry* Apoptosis / drug effects* Caspase 3 / antagonists & inhibitors, metabolism, physiology* Caspases / metabolism Cell Survival / drug effects Electrophoresis, Polyacrylamide Gel Enzyme Activation / drug effects Flow Cytometry Fluorescent Dyes Humans Indicators and Reagents Indoles Oligopeptides / pharmacology Oncogene Protein v-akt / metabolism, physiology* Phosphorylation Proto-Oncogene Proteins c-bcl-2 / physiology* U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/Fluorescent Dyes; 0/Indicators and Reagents; 0/Indoles; 0/Oligopeptides; 0/Proto-Oncogene Proteins c-bcl-2; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 47165-04-8/DAPI; EC 2.7.11.1/Oncogene Protein v-akt; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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