| Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway. | |
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MedLine Citation:
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PMID: 15132839 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: To study the mechanisms by which oridonin inhibited HeLa cell growth in vitro. METHODS: Viability of oridonin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Caspase activity was assayed using fluorometric protease assay. ICAD, Bcl-2, and Bax proteins expression were detected by Western blot analysis. RESULTS: Oridonin induced oligonucleosomal fragmentation of DNA and increased caspase-3 activity, on the other hand, reduced the expression of inhibitor of caspase-3-activated DNase (ICAD), a caspase-3 substrate, at 12 h in HeLa cells. Oridonin-induced DNA fragmentation, caspase-3 activation and down-regulation of ICAD expression were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). However, pretreatment with an inhibitor of poly (ADP-ribose) polymerase (PARP), 3, 4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), did not suppress oridonin-induced HeLa cell death. In addition, oridonin-induced apoptosis was associated with an increase in the expression of the apoptosis inducer Bax, and a significant reduction in expression of the apoptosis suppressor Bcl-2 in mitochondria. CONCLUSION: Oridonin induces HeLa cells apoptosis by altering balance of Bcl-2 and Bax protein expression and activation of caspase-3/ICAD pathway. |
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Authors:
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Chun-Ling Zhang; Li-Jun Wu; Shin-Ichi Tashiro; Satoshi Onodera; Takashi Ikejima |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Acta pharmacologica Sinica Volume: 25 ISSN: 1671-4083 ISO Abbreviation: Acta Pharmacol. Sin. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-05-10 Completed Date: 2004-08-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100956087 Medline TA: Acta Pharmacol Sin Country: China |
Other Details:
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Languages: eng Pagination: 691-8 Citation Subset: IM |
Affiliation:
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China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Apoptosis Regulatory Proteins Caspase 3 Caspases / metabolism* Cell Death / drug effects DNA Fragmentation Diterpenes / isolation & purification, pharmacology* Diterpenes, Kaurane Hela Cells Humans Plants, Medicinal / chemistry Proteins / metabolism* Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-bcl-2 / metabolism* Rabdosia / chemistry bcl-2-Associated X Protein |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/BAX protein, human; 0/Diterpenes; 0/Diterpenes, Kaurane; 0/Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 0/caspase-activated DNase inhibitor; 28957-04-2/oridonin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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