The cytotoxic effect of mistletoe lectins I, II and III on sensitive and multidrug resistant human colon cancer cell lines in vitro.
Multidrug resistance glycoprotein1 (MDR-1) eliminates amphiphilic chemotherapeutic agents out of tumour cells leading to therapeutic failures. The aim of this study was to investigate the cytotoxic effect of mistletoe lectins (MLs) I, II and III on the sensitive human colon cancer cell line HT 29(mdr-), its multidrug resistant variant HT 29(mdr+), the variant HT 29(SF1m) transfected with the MDR-1 gene and its sensitive control cell line HT 29(deltaSF). Both cell proliferation and ML binding pattern were analysed. Marked quantitative differences concerning the cytotoxic effect of the three MLs on the different cell lines were observed. All MLs showed the greatest cytotoxicity towards the HT 29(mdr+) cells, in which multidrug resistance (MDR) was induced by increasing concentrations of a MDR inducing agent. In contrast, MDR-1 and mock-transfected cells showed almost the same sensitivity towards the three MLs as the control cells (HT 29(mdr-)). FACS analysis showed that the HT 29(mdr+) cells were the cells with the highest density of ML binding sites. Thus, higher sensitivity of HT 29(mdr+) cells are not caused by the overexpression of MDR-1, but are caused by the general changes of the cellular glycosylation during the acquisition of the MDR phenotype.
Valentiner
Ursula
U
Institute for Anatomy, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. valentiner@uke.uni-hamburg.de
Pfüller
Uwe
U
Baum
Christopher
C
Schumacher
Udo
U
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006031:Glycosylation; D019073:HT29 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D010641:Phenotype; D028321:Plant Preparations; D010940:Plant Proteins; D011485:Protein Binding; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000276:Adjuvants, Immunologic; D005456:Fluorescent Dyes; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum