title: Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation.
abstract: Mistletoe extracts are used as alternative cancer treatment in addition to standard chemotherapy and radiation treatment and have an immunostimulatory and pain-relieving effect. A direct antitumour effect of mistletoe extracts against tumour cells of lymphoid origin has been linked to the D-galactoside-specific mistletoe lectin I. In this study, we investigated the cellular effect of bacterially expressed, recombinant mistletoe lectin alone or in combination with ionising radiation in a genetically defined p53-wild-type and p53-deficient E1A/ras-transformed murine tumour cells system. Downregulation of the proliferative activity and cell killing by recombinant mistletoe lectin occurred in a clear dose response (0.1-1 ng ml(-1)). Induction of apoptosis was p53-independent, but apoptosis-associated factor-1-dependent. Cellular treatment with lectin in combination with ionising radiation resulted in both p53-wild-type and p53-deficient tumour cells in an at least additive, antiproliferative effect and enhanced activation of caspase-3. Combined treatment with ionising radiation and lectin revealed a similar cytotoxic effect in human, p53-mutated adenocarcinoma cells. Thus, recombinant mistletoe lectin alone and in combination with ionising radiation bypasses often prevalent apoptotic deficiencies in treatment-resistant tumour cells.
authors.affiliation: Department of Internal Medicine, University Hospital Zurich, Raemistr. 100, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Hostanska
authors.forename: V
authors.initials: V
authors.lastname: Vuong
authors.forename: S
authors.initials: S
authors.lastname: Rocha
authors.forename: M S
authors.initials: MS
authors.lastname: Soengas
authors.forename: C
authors.initials: C
authors.lastname: Glanzmann
authors.forename: R
authors.initials: R
authors.lastname: Saller
authors.forename: S
authors.initials: S
authors.lastname: Bodis
authors.forename: M
authors.initials: M
authors.lastname: Pruschy
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D011905:Genes, ras; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D014784:Mistletoe / Q000737:chemistry; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects; D009154:Mutation / Q000235:genetics; D037121:Plant Lectins / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology*; D010940:Plant Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D054790:Ribosome Inactivating Proteins, Type 2; D012680:Sensitivity and Specificity; D014118:Toxins, Biological / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C506592:APAF1 protein, human; D017304:Annexin A5; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D011506:Proteins; D011994:Recombinant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D016159:Tumor Suppressor Protein p53; C009674:ribosome inactivating protein, Viscum; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases