Cancer letters
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Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with both immunostimulatory and DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic properties at higher concentrations. The present work examines the cytotoxic effects of VAL extracts produced from mistletoes grown on different host trees and of purified toxic proteins from VAL, such as the D-galactose-specific lectin I (ML I), the N-acetyl-D-galactosamine-specific ML II and ML III, and crude viscotoxins towards cultured human lymphocytes. The decrease in the number of cultured lymphocytes and blast cells treated with whole plant extracts from VAL was host tree-specific. ⋯ By measuring the surface expression of IL-2R alpha chains, transferrin receptors and APO-1/Fas molecules on non-apoptotic T cells, no significant changes were observed at low ML concentrations (1 ng/ml), but their decrease at higher ones. Our findings suggest that there might be at least two different ways of cell killing operative in VAL-mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell membrane with subsequent influx of Ca2+ and of the DNA intercalating dye propidium iodide and cell shrinkage. These effects might not be exclusive, as they probably occur simultaneously.
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We examined the inhibitory effect of an aqueous extract (referred to as KM-110) from Viscum album coloratum, a Korean mistletoe, on tumour metastasis produced by highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells, using experimental and spontaneous metastasis models in syngeneic mice. In experimental metastasis of B16-BL6 and colon 26-M3.1 cells, intravenous (i.v.) administration of KM-110 (100 micrograms/mouse) 1 day after tumour inoculation significantly inhibited lung metastasis of both tumour cells. The administration of KM-110 also exhibited a therapeutic effect on liver and spleen metastasis of L5178Y-ML25 lymphoma cells. ⋯ In a bioassay, the culture supernatant (KM-110-treated medium) of murine peritoneal macrophages that had been stimulated with KM-110 (1-10 micrograms/ml) for 30 min followed by 24 h incubation in fresh medium showed a strong tumour necrosis factor-alpha (TNF-alpha) activity. In addition, KM-110-treated medium significantly inhibited the growth of in vitro cultures of rat lung endothelial (RLE) cells. These results suggested that the extract of Korean mistletoe inhibits tumour metastasis caused by haematogenous as well as non-haematogenous tumour cells, and that its antimetastatic effect results from the suppression of tumour growth and the inhibition of tumour-induced angiogenesis by inducing TNF-alpha.
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Since high incidence of oral cancer in India is associated with smokeless tobacco usage, mutagenic exposure of subjects habituated to a pyrolysed tobacco product, masheri (M) and tobacco-containing betel quid (Q) was evaluated in the present study. Urinary cotinine was estimated to ascertain tobacco exposure and urine mutagenicity to Salmonella typhimurium TA98 and TA100 was used to assess mutagenic burden. ⋯ Urine mutagenicity was evident in control samples only upon treatment with S9, beta-glucuronidase or acidified nitrite. However, greater exposure of users to mutagens resulted in additional direct mutagenicity to TA100.
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Proteins from a laboratory-made oak mistletoe extract and from the commercial mistletoe preparation Iscador Quercus were cytotoxic for leukemia Molt 4 cells in culture. A 50% growth inhibition was obtained with 0.1 microgram/ml proteins for the mistletoe extract and 0.025 microgram/ml for Iscador. On cation exchange chromatography, cytotoxic proteins from the mistletoe extract were mainly eluted at the same positions as purified lectins, while those of Iscador were eluted at the positions of viscotoxins. The data are discussed in relation to the pharmacological activities of the mistletoe protein complexes described in the literature.
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Using a combination of gel filtration and paper chromatography, a tumour reducing component from mistletoe extract (Iscador) was isolated and identified to be a peptide of approximate molecular weight 5000. The isolated peptide reduced the solid tumour induced by Dalton's lymphoma ascites tumour cells (DLA cells) in mice. The isolated component was very cytotoxic to the DLA cells but was not cytotoxic to normal lymphocytes, indicating a cell dependent specificity.