| Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells. | |
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MedLine Citation:
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PMID: 12175527 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Se-methylselenocysteine (Se-MSC) is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis, but its mechanism of action is still not well understood. The present study was designed to assess the mechanism of Se-MSC on the induction of apoptosis in SKOV-3 ovarian cancer cells. Se-MSC displayed strong inhibitory effects on cell proliferation and viability of SKOV-3 cells in dose and time dependent manners and induced apoptosis. Investigation of the mechanism of Se-MSC-induced apoptosis revealed that treatment with Se-MSC produced morphological features of apoptosis and DNA fragmentation. This was associated with caspase-3 activation and cleavage of poly(ADP-ribose) polymerase and phospholipase C-gamma1 proteins. However, SKOV-3 cells treated with Se-MSC did not demonstrate cytochrome c accumulation in the cytosol during apoptosis induction. Pretreatment of cells with the caspase inhibitors (z-VAD-fmk and DEVD-CHO) prevented Se-MSC-induced apoptosis. These results suggested that Se-MSC induces apoptosis through cytochrome c-independent caspase-3 activation in SKOV-3 cells. In late stage of apoptosis, p18kDa fragment of Bax was generated with the down-regulation of the expressions of survivin, X-linked inhibitor of apoptosis protein, and human inhibitor of apoptosis protein 1 following Se-MSC treatment, suggesting that the modulation of Bax and IAP (inhibitors of apoptosis) family proteins play some role in Se-MSC-mediated apoptosis. Pre-treatments of z-VAD-fmk and the calpain inhibitor, calpeptin inhibited Bax cleavage. These results suggested that Bax cleavage is mediated by calpain, and calpain activation may be a caspase-dependent one. Taken together, the chemopreventive effects of Se-MSC may be related in part to the caspase-3 activation, the down-regulation of IAP family proteins, and Bax cleavage mediated by caspase-dependent calpain activation. |
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Authors:
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Jun-Kyu Yeo; Soon-Do Cha; Chi-Heum Cho; Sang-Pyo Kim; Jae-We Cho; Won-Ki Baek; Min-Ho Suh; Taeg Kyu Kwon; Jong-Wook Park; Seong-Il Suh |
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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: Cancer letters Volume: 182 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2002-08-14 Completed Date: 2002-08-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 83-92 Citation Subset: IM |
Affiliation:
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Department of Gynecology and Obstetrics, Keimyung University School of Medicine, Daegu, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anticarcinogenic Agents
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pharmacology* Apoptosis / drug effects* Calpain / physiology* Caspases / physiology* Cysteine / analogs & derivatives*, pharmacology* Cytochrome c Group / physiology Enzyme Activation Female Humans Inhibitor of Apoptosis Proteins Organoselenium Compounds / pharmacology* Ovarian Neoplasms / pathology Poly(ADP-ribose) Polymerases / metabolism Proteins / analysis Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-bcl-2 / analysis Tumor Cells, Cultured bcl-2-Associated X Protein |
| Chemical | |
Reg. No./Substance:
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0/Anticarcinogenic Agents; 0/BAX protein, human; 0/Cytochrome c Group; 0/Inhibitor of Apoptosis Proteins; 0/Organoselenium Compounds; 0/Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 2574-71-2/selenomethylselenocysteine; 52-90-4/Cysteine; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Calpain; EC 3.4.22.-/Caspases |
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