| Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases. | |
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MedLine Citation:
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PMID: 11295044 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The therapeutic efficacies of bile acids, such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA), have been widely demonstrated in various liver diseases, suggesting that they might protect hepatocytes against common mechanisms of liver damage. Although they have been shown to prevent apoptotic cell death in certain cell lines, we have previously reported that a novel derivative (HS-1030) of UDCA significantly inhibited cell growth and induced apoptosis in cancer cells. To develop more effective agents, we synthesized several derivatives, named HS-1183, HS-1199 and HS-1200, based on the structure of UDCA and CDCA, and investigated them for anti-proliferative activity in Jurkat cells, a human leukemic T cell line. Whereas UDCA and CDCA had no significant effects on the growth of Jurkat cells in the concentration range tested, both HS-1199 and HS-1200 completely inhibited the cell proliferation, and HS-1183 showed only a weak inhibitory activity. Furthermore, chromatin condensation, DNA ladder formation and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) were observed after treatment of novel bile acids, indicating the occurrence of apoptotic cell death, which was associated with down-regulation of caspase-3 and -8. The apoptotic manifestations such as PARP cleavage and DNA fragmentation were abolished in the presence of the tripeptide caspase inhibitor zVAD-fmk or the specific caspase-3 inhibitor DEVD-fmk. Our data thus demonstrate that novel bile acid derivatives-induced apoptosis of leukemic T cells is dependent on caspase activation. |
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Authors:
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Y H Choi; E O Im; H Suh; Y Jin; W H Lee; Y H Yoo; K W Kim; N D Kim |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of oncology Volume: 18 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2001 May |
Date Detail:
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Created Date: 2001-04-11 Completed Date: 2001-06-07 Revised Date: 2012-02-02 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 979-84 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Pusan 614-052, Korea. choiyh@hyomin.dongeui.ac.kr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Blotting, Western Caspase 3 Caspase 8 Caspase 9 Caspases / antagonists & inhibitors, metabolism* Cell Survival / drug effects Chenodeoxycholic Acid / analogs & derivatives, pharmacology* Cholagogues and Choleretics / pharmacology* DNA Fragmentation / drug effects DNA, Neoplasm / drug effects, genetics, metabolism Dose-Response Relationship, Drug Down-Regulation Gastrointestinal Agents / pharmacology* Humans Jurkat Cells / drug effects Leukemia / metabolism, pathology, prevention & control* Phosphorylation / drug effects Poly(ADP-ribose) Polymerases / metabolism Tumor Cells, Cultured Tumor Suppressor Protein p53 / drug effects, physiology* Ursodeoxycholic Acid / analogs & derivatives, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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K01 DK083336-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cholagogues and Choleretics; 0/DNA, Neoplasm; 0/Gastrointestinal Agents; 0/Tumor Suppressor Protein p53; 128-13-2/Ursodeoxycholic Acid; 474-25-9/Chenodeoxycholic Acid; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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