| A lysosomal-mitochondrial death pathway is induced by solamargine in human K562 leukemia cells. | |
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MedLine Citation:
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PMID: 20647040 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Solamargine (SM), a steroidal alkaloid glycoside from Solanum nigrum L., displayed a superior cytotoxicity to many human tumor cells. Further investigation with human K562 leukemia cells found that SM could induce an early lysosomal rupture within 2h as assessed by acridine-orange relocation and alkalinization of lysosomes. Intracellular lysosomal rupture is also confirmed with the release of cathepsin B to cytosol detected by western blot. Subsequent mitochondrial damage including mitochondrial membrane permeabilization detected by decrease membrane potential as well as the release of cytochrome c from mitochondria was also observed. The cellular Ca(2+) overload is more pronounced in SM-treated cells. Cells exposed to 10 microM SM for 30 min showed a maximum 7-fold increase in intracellular calcium concentration compared with vehicle-treated controls. The down-expression of Bcl-2, up-regulation of Bax, caspase-3 and caspase-9 activities followed by above changes revealed that the cytotoxicity of SM was involved in a lysosomal-mitochondrial death pathway induced by SM. |
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Authors:
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Lingmei Sun; Ying Zhao; Xia Li; Huiqing Yuan; Aixia Cheng; Hongxiang Lou |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-18 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 24 ISSN: 1879-3177 ISO Abbreviation: Toxicol In Vitro Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-31 Completed Date: 2010-12-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 1504-11 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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School of Pharmaceutical Sciences, Shandong University, Jinan, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Calcium / metabolism Caspases / genetics, metabolism Cathepsin B / metabolism Cell Survival / drug effects Gene Expression Regulation Humans K562 Cells Leukemia, Erythroblastic, Acute / drug therapy*, metabolism, pathology Lysosomes / drug effects*, metabolism Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects* Mitochondrial Membranes / drug effects Permeability / drug effects Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism Solanaceous Alkaloids / pharmacology* Tumor Stem Cell Assay bcl-2-Associated X Protein / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/BAX protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/Solanaceous Alkaloids; 0/bcl-2-Associated X Protein; 3671-38-3/beta-solamarine; 7440-70-2/Calcium; EC 3.4.22.-/Caspases; EC 3.4.22.1/Cathepsin B |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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