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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Animals
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Annexin A5 / metabolism
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Apoptosis / drug effects*
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Apoptotic Protease-Activating Factor 1
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Blotting, Western
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Caspase 3
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Caspases / metabolism
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Cell Division / drug effects
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Cell Division / radiation effects
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Fibroblasts / metabolism
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Genes, ras
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Humans
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Membrane Potentials / drug effects
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Membrane Potentials / radiation effects
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Mice
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Mistletoe / chemistry
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Mitochondria / drug effects
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Mitochondria / radiation effects
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Mutation / genetics
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Plant Lectins / pharmacology*
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Plant Preparations / pharmacology*
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Plant Proteins*
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Proteins / genetics
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Proteins / metabolism
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Radiation, Ionizing
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Ribosome Inactivating Proteins, Type 2
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Sensitivity and Specificity
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Toxins, Biological / pharmacology*
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism*
Substances
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APAF1 protein, human
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Annexin A5
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Apaf1 protein, mouse
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Apoptotic Protease-Activating Factor 1
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Plant Lectins
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Plant Preparations
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Plant Proteins
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Proteins
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Recombinant Proteins
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Ribosome Inactivating Proteins, Type 2
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Toxins, Biological
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Tumor Suppressor Protein p53
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ribosome inactivating protein, Viscum
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CASP3 protein, human
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Casp3 protein, mouse
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Caspase 3
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Caspases