| Norcantharidin preferentially induces apoptosis in human leukemic Jurkat cells without affecting viability of normal blood mononuclear cells. | |
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MedLine Citation:
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PMID: 17442474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Norcantharidin (NCTD) is known to have anti-cancer potentials. The aim of this study was to assess the apoptosis-inducing effect of NCTD on human leukemic Jurkat cells. We found that NCTD preferentially inhibited the growth of Jurkat cells in a dose- and time-dependent manner, but not the growth of normal blood mononuclear cells (MNC). Pretreatment with agonistic (CH-11) and antagonistic (ZB4) Fas antibodies on Jurkat cells showed that NCTD-induced apoptosis might not involve Fas-FasL signaling. Flow cytometric assay of Jurkat cells treated with NCTD showed a markedly increased sub-G1 DNA phase and cell cycle arrest at S phase. Western blot analysis of NCTD-treated cells showed increased expressions of cytochrome c, active caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase (PARP), but the expressions of Bcl-2, Bax and apoptosis-inducing factor were not increased. The transcription factor STAT1 was translocated from cytosol to nucleus. Pancaspase inhibitor z-VAD-FMK not only limited the level of sub-G1 phase, but also prevented the degradation of PARP in NCTD-treated cells. The NCTD-induced cell cycle arrest and apoptosis were mediated through the regulation of ataxia-telangiectasia mutated (ATM), rather than P63 protein. The conditioned medium produced from human MNC (NCTD-MNC-CM) increased the percentage of apoptotic cells and the expression of PARP cleavage in Jurkat cells. Protein array assay of NCTD-MNC-CM showed 32.4- and 6.2-folds increases in TNF-alpha and GM-CSF, respectively, and the expression of MCP-1, GRO, RANTES and IL-10 was decreased. We conclude that NCTD can induce apoptosis in human leukemic Jurkat cells via a caspase-dependent pathway without affecting the viability of normal MNC, and that the apoptosis-inducing effect of NCTD can also be achieved by soluble cytokines produced from peripheral MNC. |
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Authors:
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Hui-Fen Liao; Shu-Li Su; Yu-Jen Chen; Chin-Hung Chou; Cheng-Deng Kuo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-12 |
Journal Detail:
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Title: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Volume: 45 ISSN: 0278-6915 ISO Abbreviation: Food Chem. Toxicol. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-08-01 Completed Date: 2007-10-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8207483 Medline TA: Food Chem Toxicol Country: England |
Other Details:
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Languages: eng Pagination: 1678-87 Citation Subset: IM |
Affiliation:
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Laboratory of Biophysics, Department of Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects* Bicyclo Compounds, Heterocyclic / pharmacology* Blotting, Western Caspases / metabolism Cell Proliferation Cell Survival / drug effects Cytokines / biosynthesis DNA / metabolism Dose-Response Relationship, Drug Flow Cytometry Humans Jurkat Cells / drug effects* Leukocytes, Mononuclear / cytology, drug effects*, metabolism MAP Kinase Signaling System / drug effects S Phase / drug effects* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Bicyclo Compounds, Heterocyclic; 0/Cytokines; 5442-12-6/norcantharidin; 9007-49-2/DNA; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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