Document Detail


Effects of mistletoe (Viscum album L.) extracts Iscador on cell cycle and survival of tumor cells.
MedLine Citation:
PMID:  16927529     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The molecular and cellular mechanisms by which mistletoe (Viscum album L.) extracts exert cytotoxic and immunomodulatory anti-tumoral effects are largely unknown. In this study the hypothesis that Iscador preparations induce tumor regression by cell cycle inhibition and/or interference with apoptotic signaling pathways in cancer cells was investigated. Also a possible effect on angiogenesis, which is a prerequisite for tumor growth in vivo, is studied in endothelial cell cultures. Furthermore, it was examined which apoptotic signaling route(s) is (are) activated by Iscador by studying specific pro-apoptotic proteins in cultured cells. To characterize these properties, 9 human cancer cell lines of different origin, one epidermis derived cell line and 2 endothelial cell cultures were incubated with different concentrations of Iscador Quercus Spezial and Iscador Malus Spezial. Cell cycle kinetic parameters were measured by bromodeoxyuridine (BrdU) pulse labeling and tubulin staining. Apoptotic responses were detected by M30 Cyto-Death or Annexin V/propidium iodide assays. Characterization of the apoptotic pathway(s) was performed by staining cells for amongst others active caspase 3 and cytochrome C (mitochondrial pathway), as well as active caspase 8 (death receptor pathway). The sensitivity to Iscador treatment varies strongly between different cell lines and also ing those derived from small cell lung cancer, and adenocarcinoma of the lung and breast, as well as endothelial cell cultures, Iscador caused early cell cycle inhibition followed by apoptosis in a dose dependent manner. Amongst the low responders are cell lines derived from colorectal carcinoma. In general Iscador Malus exerted a stronger response than Iscador Quercus. Apoptosis was induced by activating the mitochondrial but not the death receptor dependent pathway, at least in case of Iscador Quercus. Iscador Malus also seemed to induce apoptosis via the death receptor route, which may explain the higher sensitivity of cancer and endothelial cells to this preparation.
Authors:
Marjan Harmsma; Monique Ummelen; Wendy Dignef; Karel Jan Tusenius; Frans C S Ramaekers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  56     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-08-24     Completed Date:  2006-09-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  474-82     Citation Subset:  IM    
Affiliation:
MUbio Products B.V, Maastricht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Annexin A5 / pharmacology
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Bromodeoxyuridine / diagnostic use
Cell Cycle / drug effects*
Cell Division / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Coloring Agents
DNA, Neoplasm / biosynthesis
Endothelial Cells / drug effects
Enzyme Inhibitors / pharmacology
Humans
Microtubules / drug effects,  ultrastructure
Plant Extracts / pharmacology*
Plant Proteins / pharmacology*
Propidium
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Antineoplastic Agents, Phytogenic; 0/Coloring Agents; 0/DNA, Neoplasm; 0/Enzyme Inhibitors; 0/Plant Extracts; 0/Plant Proteins; 0/viscum album peptide; 36015-30-2/Propidium; 59-14-3/Bromodeoxyuridine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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