title: Impact of Mistletoe Triterpene Acids on the Uptake of Mistletoe Lectin by Cultured Tumor Cells.
abstract: Complementary treatment possibilities for the therapy of cancer are increasing in demand due to the severe side effects of the standard cytostatics used in the first-line therapy. A common approach as a complementary treatment is the use of aqueous extracts of Viscum album L. (Santalaceace). The therapeutic activity of these extracts is attributed to Mistletoe lectins which are Ribosome-inactivating proteins type II. Besides these main constituents the extract of Viscum album L. comprises also a mixture of lipophilic ingredients like triterpene acids of the oleanane, lupane and ursane type. However, these constituents are not contained in commercially available aqueous extracts due to their high lipophilicity and insolubility in aqueous extraction media. To understand the impact of the extract ingredients in cancer therapy, the intracellular uptake of the mistletoe lectin I (ML) by cultured tumor cells was investigated in relation to the mistletoe triterpene acids, mainly oleanolic acid. Firstly, these hydrophobic triterpene acids were solubilized using cyclodextrins ("TT" extract). Afterwards, the uptake of either single compounds (isolated ML and the aqueous "viscum" extract) or in combination with the TT extract (ML+TT, viscumTT), was analyzed. The uptake of ML was studied inTHP-1-, HL-60-, 143B- and Ewing TC-71-cells and determined after 30, 60 and 120 minutes by an enzyme linked immunosorbent assay which quantifies the A-chain of the hololectin. It could be shown that the intracellular uptake after 120 minutes amounted to 20% in all cell lines after incubation with viscumTT. The studies further revealed that the uptake in THP-1-, HL-60- and Ewing TC-71-cells was independent of the addition of TT extract. Interestingly, the uptake of ML by 143B-cells could only be measured after addition of triterpenes pointing to resistance to mistletoe lectin.
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutical Biology, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mulsow
authors.affiliation: Department of Biotechnology, Mannheim University of Applied Sciences, Mannheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Enzlein
authors.affiliation: Department of Paediatrics, Division of Oncology / Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Catharina
authors.initials: C
authors.lastname: Delebinski
authors.affiliation: Birken AG, Niefern-Oeschelbronn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jaeger
authors.affiliation: Department of Paediatrics, Division of Oncology / Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Seifert
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutical Biology, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Melzig
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D037121:Plant Lectins / Q000378:metabolism; D054790:Ribosome Inactivating Proteins, Type 2 / Q000378:metabolism*; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D014118:Toxins, Biological / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D028182:Viscum album / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D037121:Plant Lectins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D014315:Triterpenes; C488862:mistletoe lectin I