| Isoangustone A present in hexane/ethanol extract of Glycyrrhiza uralensis induces apoptosis in DU145 human prostate cancer cells via the activation of DR4 and intrinsic apoptosis pathway. | |
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MedLine Citation:
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PMID: 20229524 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glycyrrhiza uralensis (licorice) is one of the most frequently prescribed ingredients in Oriental medicine, and licorice extract has been shown to exert anti-carcinogenic effects. However, its use as a cancer chemopreventive agent is rather limited, due to the fact that its principal component, glycyrrhizin, is known to induce hypertension. This study determined the effects of a hexane/ethanol extract of G. uralensis (HEGU), which contains undetectable amounts of glycyrrhizin, on the apoptosis of androgen-insensitive DU145 cells. HEGU induced apoptosis and increased the levels of cleaved caspase-9, caspase-7, caspase-3 and poly (ADP-ribose) polymerase (PARP). HEGU also induced mitochondrial membrane depolarization and cytochrome c release to the cytosol. HEGU increased the levels of Fas, death receptor 4 (DR4), cleaved caspase-8, Mcl-1S, and truncated Bid proteins. A caspase-8 inhibitor suppressed HEGU-induced apoptosis. An active fraction of HEGU was separated via column chromatography and the structure of the active compound isoangustone A was identified via 1H-NMR and 13C-NMR. Isoangustone A increased apoptotic cells, the cleavage of PARP and caspases, and the levels of DR4 and Mcl-1S. Transfection with DR4 small interfering RNA attenuated HEGU- and isoangustone A-induced apoptosis. These results demonstrate that the activation of DR4 contributes to HEGU- and isoangustone A-induced apoptosis of DU145 cells. |
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Authors:
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Mi Ra Seon; Soon Sung Lim; Hyun Ju Choi; So Young Park; Han Jin Cho; Jin-Kyu Kim; Jongdai Kim; Dae Young Kwon; Jung Han Yoon Park |
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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: 54 ISSN: 1613-4133 ISO Abbreviation: Mol Nutr Food Res Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-08 Completed Date: 2011-01-27 Revised Date: - |
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: 1329-39 Citation Subset: IM |
Affiliation:
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Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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chemistry,
isolation & purification,
pharmacology* Apoptosis / drug effects* Caspases / antagonists & inhibitors, metabolism Cell Line, Tumor Cell Survival / drug effects Glycyrrhiza uralensis / chemistry* Humans Isoflavones / chemistry, isolation & purification, pharmacology* Male Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects, enzymology Molecular Structure Permeability / drug effects Plant Extracts / chemistry, pharmacology* Poly(ADP-ribose) Polymerases / metabolism Prostatic Neoplasms / drug therapy*, metabolism, pathology Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Small Interfering Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics, metabolism* Signal Transduction / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Isoflavones; 0/Plant Extracts; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/TNFRSF10A protein, human; 0/isoangustone A; 0/myeloid cell leukemia sequence 1 protein; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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