| Induction of apoptosis by takrisodokyeum through generation of hydrogen peroxide and activation of caspase-3 in HL-60 cells. | |
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MedLine Citation:
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PMID: 12899915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Takrisodokyeum (TRSDY), a Chinese herbal medicine, has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that TRSDY induced apoptosis in HL-60 cells as evidenced by both a characteristic ladder pattern of discontinuous DNA fragments and an increase of annexin V+/PI- stained cell population. Our data demonstrated that TRSDY-induced apoptotic cell death was accompanied by activation of caspase-3 and cleavages of its substrates, poly(ADP-ribose) polymerase (PARP) and RhoGDP dissociation inhibitor (RhoGDI-2; also called D4-GDI) in a time- and concentration-dependent manner. Caspase-3 inhibitor, but not caspase-1 inhibitor, prevented TRSDY-induced apoptosis. Furthermore, treatment with TRSDY increased the production of intracellular hydrogen peroxide and pretreatment of cells with anti-oxidants conferred complete protection against hydrogen peroxide generation and subsequent caspase-3 activation. Taken together, these results suggest that TRSDY induces hydrogen peroxide generation, which, in turn, causes activation of caspase-3, degradation of PARP and D4-GDI, and eventually leads to apoptotic cell death. |
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Authors:
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Kang-Beom Kwon; Eun-Kyung Kim; Byung-Cheul Shin; Eun-A Seo; Jin-Woo Park; Jong-Suk Kim; Byung-Hyun Park; Do-Gon Ryu |
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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: Life sciences Volume: 73 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-08-05 Completed Date: 2003-09-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: England |
Other Details:
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Languages: eng Pagination: 1895-906 Citation Subset: IM |
Affiliation:
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Department of Physiology, School of Oriental Medicine, Won-Kwang University, Iksan, Chonbuk 570-749, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Annexin A5
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analysis Antineoplastic Agents / pharmacology* Apoptosis / drug effects Caspase 3 Caspases / metabolism* Cell Survival / drug effects DNA Fragmentation Dose-Response Relationship, Drug Drugs, Chinese Herbal / pharmacology* Flow Cytometry HL-60 Cells / drug effects*, enzymology, pathology Humans Hydrogen Peroxide / metabolism* Leukemia Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; 0/Antineoplastic Agents; 0/Drugs, Chinese Herbal; 0/Proteins; 0/takrisodokyeum; 7722-84-1/Hydrogen Peroxide; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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