| Geraniin-mediated apoptosis by cleavage of focal adhesion kinase through up-regulation of Fas ligand expression in human melanoma cells. | |
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MedLine Citation:
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PMID: 18435487 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Geraniin, a form of tannin separated from geranium, causes cell death through induction of apoptosis; however, cell death characteristics for geraniin have not yet been elucidated. Here, we investigated the mechanism of geraniin-induced apoptosis in human melanoma cells and demonstrated that geraniin was able to induce cell apoptosis in a concentration- and time-dependent manner. We also examined the signaling pathway related to geraniin-induced apoptosis. To clarify the relationship between focal adhesion kinase (FAK) and geraniin-induced apoptosis, we treated human melanoma cells with geraniin and found that this resulted dose- and time-dependent degradation in FAK. However, FAK cleavage was significantly inhibited when cells were pretreated with a selective inhibitor of caspase-3 (Ac-Asp-Glu-Val-Asp-CHO). Here, we demonstrated for the first time that geraniin triggered cell death by caspase-3-mediated cleavage of FAK. There were two possible mechanisms for activating caspase-3, mitochondria-mediated and receptor-mediated apoptosis. To confirm the geraniin-relevant signaling pathway, using immunoblot analysis we found that geraniin-induced apoptosis was associated with the up-regulation of Fas ligand expression, the activation of caspase-8, the cleavage of Bid, and the induction of cytochrome c release from mitochondria to the cytosol. Treatment with geraniin caused induction of caspase-3 activity in a dose- and time-dependent manner followed by proteolytic cleavage of poly-(ADP-ribose) polymerase, and DNA fragmentation factor 45. The geraniin-induced apoptosis may provide a pivotal mechanism for its cancer-chemopreventive action. |
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Authors:
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Jang-Chang Lee; Chih-Yen Tsai; Jung-Yie Kao; Ming-Ching Kao; Shih-Chang Tsai; Chih-Shiang Chang; Li-Jiau Huang; Sheng-Chu Kuo; Jen-Kun Lin; Tzong-Der Way |
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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: Molecular nutrition & food research Volume: 52 ISSN: 1613-4133 ISO Abbreviation: Mol Nutr Food Res Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-11 Completed Date: 2008-08-20 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101231818 Medline TA: Mol Nutr Food Res Country: Germany |
Other Details:
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Languages: eng Pagination: 655-63 Citation Subset: IM |
Affiliation:
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Graduate institute of Pharmaceutical Chemistry, College of Pharmacy, China Medical University, Taichung, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anticarcinogenic Agents
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pharmacology Apoptosis / drug effects* BH3 Interacting Domain Death Agonist Protein / metabolism Caspase 3 / antagonists & inhibitors Caspase 8 / metabolism Cell Line, Tumor Cytochromes c / metabolism Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Fas Ligand Protein / genetics* Focal Adhesion Protein-Tyrosine Kinases / metabolism* Glucosides / metabolism, pharmacology* Humans Hydrolyzable Tannins / metabolism, pharmacology* Melanoma / metabolism* Up-Regulation / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Anticarcinogenic Agents; 0/BH3 Interacting Domain Death Agonist Protein; 0/Enzyme Inhibitors; 0/Fas Ligand Protein; 0/Glucosides; 0/Hydrolyzable Tannins; 60976-49-0/Geraniin; 9007-43-6/Cytochromes c; EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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