| Apoptosis induction of human leukemia U937 cells by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill. | |
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MedLine Citation:
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PMID: 20034537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We compared the pro-apoptotic effect of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in U937 human promyelocytic leukemia cells in vitro. Gomisin N, but not gomisin A, inhibited cell growth in a dose-dependent manner, which was associated with the induction of apoptosis. The increase in apoptosis that was induced by gomisin N was correlated with down-regulation of anti-apoptotic Bcl-2 expression, a decrease in the mitochondrial membrane potential (MMP) and a release of cytochrome c from the mitochondria into the cytosol. Furthermore, gomisin N induced the proteolytic activation of caspase-9 and -3 and a concomitant degradation of poly(ADP-ribose) polymerase. However, caspase-8 was not activated and cleavage of Bid was not observed in gomisin N-treated U937 cells. The cytotoxic effects and apoptotic characteristics induced by gomisin N were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role that caspase-3 plays in the process. We conclude that gomisin N induces the apoptosis of U937 cells through a signaling cascade of mitochondria-mediated intrinsic caspase pathways and gomisin N may be a useful chemotherapeutic agent. |
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Authors:
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Jong-Hwan Kim; Young-Whan Choi; Cheol Park; Cheng-Yun Jin; You Jin Lee; Da Jung Park; Sun Guen Kim; Gi-Young Kim; Il-Whan Choi; Won-Deuk Hwang; Yong Kee Jeong; Se-Kwon Kim; Yung Hyun Choi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-23 |
Journal Detail:
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Title: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Volume: 48 ISSN: 1873-6351 ISO Abbreviation: Food Chem. Toxicol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-22 Completed Date: 2010-06-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8207483 Medline TA: Food Chem Toxicol Country: England |
Other Details:
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Languages: eng Pagination: 807-13 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2009 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Oriental Medicine, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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pharmacology* Apoptosis / drug effects* Blotting, Western Caspase 3 / antagonists & inhibitors, metabolism Cell Proliferation / drug effects Cell Survival / drug effects Cyclin D1 / metabolism Cyclooctanes / pharmacology Cytochromes c / metabolism DNA Fragmentation Dioxoles / pharmacology Flow Cytometry Fruit / chemistry G1 Phase / drug effects Humans Lignans / pharmacology* Mitochondria / drug effects, metabolism Polycyclic Compounds / pharmacology* Schisandra / chemistry* U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Cyclooctanes; 0/Dioxoles; 0/Lignans; 0/Polycyclic Compounds; 136601-57-5/Cyclin D1; 58546-54-6/schizandrol B; 64121-95-5/schizandrin B; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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