| Reactive oxygen species-mediated induction of apoptosis by a plant alkaloid 6-methoxydihydrosanguinarine in HepG2 cells. | |
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MedLine Citation:
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PMID: 15904897 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have found in the previous study that 6-methoxydihydrosanguinarine (6ME), a benzophenanthridine alkaloid isolated from Hylomecon species, may have potential as a chemotherapeutic agent. However, the mechanisms of 6ME-induced cell death have not been investigated. The purpose of the present study was to determine the apoptosis-inducing potential of 6ME in human hepatocarcinoma HepG2 cells and the role of reactive oxygen species in 6ME-induced apoptosis. It can be concluded from the results that 6ME inhibits the growth of HepG2 cells in a concentration- and time-dependent manner (IC50=3.8+/-0.2 microM following 6 h incubation). Treatment of HepG2 cells with 6ME resulted in the release of mitochondrial cytochrome c followed by the activation of caspase proteases, and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. 6ME increased the expression of p53 and bax and decreased the expression of bcl-2. The cytotoxic effect of 6ME is mediated by the time-dependent generation of reactive oxygen species. Our results also show that preincubation of HepG2 cells with vitamin C decreased the expression of p53 and bax and inhibited the release of cytochrome c, activation of downstream caspase and the cleavage of poly(ADP-ribose) polymerase, thus inhibiting the apoptosis inducing effect of 6ME. |
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Authors:
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Hu-Quan Yin; Young-Ho Kim; Chang-Kiu Moon; Byung-Hoon Lee |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical pharmacology Volume: 70 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-06-20 Completed Date: 2005-08-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 242-8 Citation Subset: IM |
Affiliation:
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College of Pharmacy, Seoul National University, San 56-1 Sillim-dong, Gwanak-gu, Seoul 151-742, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkaloids
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isolation & purification,
pharmacology* Apoptosis / drug effects*, physiology Benzophenanthridines Cell Line, Tumor Humans Isoquinolines Phenanthridines / isolation & purification, pharmacology* Plant Extracts / isolation & purification, pharmacology Reactive Oxygen Species / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/6-methoxydihydrosanguinarine; 0/Alkaloids; 0/Benzophenanthridines; 0/Isoquinolines; 0/Phenanthridines; 0/Plant Extracts; 0/Reactive Oxygen Species |
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