| Activation of p38 MAPK by damnacanthal mediates apoptosis in SKHep 1 cells through the DR5/TRAIL and TNFR1/TNF-α and p53 pathways. | |
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MedLine Citation:
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PMID: 20951126 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The effect of the natural compound damnacanthal from Morinda citrifolia on SKHep 1 cell growth regulation was investigated. Treatment of SKHep 1 cells with damnacanthal for 24h indicated a dose-dependent antiproliferative activity. Damnacanthal seems to be selective for tumor cell lines, since there is only minimal toxicity against normal hepatocyte cells (FL83B). This is first demonstration that damnacanthal-mediated apoptosis involves the sustained activation of the p38 MAPK pathway, leading to the transcription of the death receptor family genes encoding DR5/TRAIL and TNF-R1/TNF-α genes as well as the p53-regulated Bax gene. The damnacanthal-mediated expression of DR5/TRAIL and TNF-R1/TNF-α results in caspase 8 activation, leading to Bid cleavage. In turn, activated Bid, acting with p53-regulated Bax, leads to cytochrome c released from mitochondria into the cytoplasm. Combined activation of the death receptors and mitochondrial pathways results in activation of the downstream effecter caspase 3, leading to cleavage of PARP. TRAIL- and TNF-α-mediated damnacanthal-induced apoptosis could be suppressed by treatment with caspase inhibitors as well as soluble death receptors Fc:DR5 and Fc:TNF-R1 chimera. Taken together, this study provided first evidence demonstrating that TRAIL-, TNF-α-, and p53-mediated damnacanthal-induced apoptosis require the activation of p38 MAPK and mitochondrion-mediated caspase-dependent pathways. |
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Authors:
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Feng-Lang Lin; Jue-Liang Hsu; Chang-Hung Chou; Wen-Jun Wu; Chi-I Chang; Hung-Jen Liu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-14 |
Journal Detail:
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Title: European journal of pharmacology Volume: 650 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 120-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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