Viscotoxin

Figure 3 Comparison of several thionins reveals their structural similarity. The structures are color coded for their secondary structure, cyan a-helix, red /3-strand, magenta random coil/turn. (a) a-Purothionin (2plh) and (b) /3-purothionin (1 bhp) have four disulfide bonds, (c) Crambin (1 ejg) has three disulfide bonds. Despite its thionin fold it lacks antimicrobial or other toxic activity, (d) An overlay of crambin (1ejg, black), a-purothionin (2plh, red), /3-purothionin (1 bhp, orange), viscotoxin A3 (ledO, magenta), and viscotoxin B (Ijmp, cyan) from Viscum album reveals the conserved structure of the peptide backbone.

B17. Bussing, A., Vervecken, W, Wagner, M., Wagner, B., Pfuller, U., and Schietzel, M., Expression of mitochondrial Apo2.7 molecules and caspase-3 activation in human lymphocytes treated with the ribosome-inhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins. Cytometry 37, 133-139 (1999). 

N.A. Galactoside-specific lectin, lignans, viscotoxin, choline, alkaloids, resin, acetylcholine, protein, flavonoids, caffeic acid, viscin, carotenoids.99100 181 Lower blood pressure, stimulate heart action, and treat arteriosclerosis. 

Figure 6 Three-dimensional structure of viscotoxin B (1JMP) from mistletoe (Viscum album).

Viscum viscotoxin Viscum album (misdetoe) Apoptotic (DNA... 

Viscum Viscotoxins A1, A2, Viscum album (mistletoe) — leakage aggregation antifungal] PM [permeabilize PM ... 

Viscotoxin, a basic peptide of molecular weight ca. 9000 (Samulsson, 1961), moves unretarded in strongly cross-linked gels such as Sephadex G-25 (Fig. 4a) (in phosphate buffer, ionic strength 0.05, pH 6.8. When filtered under similar conditions in weakly cross-linked dextran, viscotoxin behaves quite differently (Fig. 4b). In fact it moves behind isoleucine. The gel of the first kind can be used to remove solutes of lower molecular size, the purification being based on molecular exclusion. Filtration in the second kind of gel may be used not only for separating solutes of different molecular size but also to separate peptides and other substances of similar molecular size when they differ in certain structural features. 

The stems and leaves of Viscum album (all heal, bird hme, devil s fuge, golden bough, mistletoe) contain alkaloids, viscotoxins, and lectins. While the toxicity of... 

Viscum contain lectins that are cytotoxic by inhibiting protein synthesis on the ribosomal level in a manner similar to the toxalbumins ricin and abrin. Viscotoxin and phoratoxin are cardiac toxins and vasoconstrictors. Both produced reflex bradycardia, negative inotropic effects, and, in high doses, vasoconstriction of skin and skeletal muscle vessels in animals. 

It has been suggested that the lectins and viscotoxins are responsible for the antitumour activity. The viscotoxins (m.w. about 5,000) inhibit cell growth, but are 100 times less active than the lectins. 

Olson, T, Samuelsson, G. Purification of viscotoxin Aox2 from the European Mistletoe (Viscum album L.) by chromatography on DEAE-cellulose. Acta Chem. Scand. 1970, 24, 720-721... 

The extracts of mistletoe have been shown to inhibit the growth of a variety of animal and human cancer cells in vitro and tumor growth in vivo in a number of animal models. Iscador was found to be selectively cytotoxic to tumor cells while causing no damage to cells of the iimnune system. The antitumor effects of mistletoe reportedly depend on several factors, like the type of host tree, the time of collection during the year, and the manufacturing process. The active principles are found to be lectins, viscotoxins, and alkaloids. 

RoseU, S., and G. Samuelsson. 1966. Effect of mistletoe viscotoxin and phoratoxin on blood circulation. Toxicon 4(2) 107-108. SpUler, H.A., D.B. Willias, S.E. Gorman, and J. Sanjftleban. 1996. Retrospective study of mistletoe ingestion. /. Toxicol. Clin. Toxicol. 34(4) 405-408. 

The LD50 of viscotoxins is 0.5 mg/kg after intraperito-neal administration to mice and 0.1 mg/kg after intravenous administration to cats. Sublethal doses were reported to cause hypotension, bradycardia, and negative inotropic effects (Samuelsson 1974). 

Bauer, C., T. Oppel, F. Rueff, and B. Przybilla. 2005. Anaphylaxis to viscotoxins of mistletoe (Viscum album) extracts. Ann. Allergy Asthma Immunol. 94(l) 86-89. 

Olson, J. and G. Samuelsson, The amino acid sequence of viscotoxin A2 from the European mistletoe (Viscum album), Acta Chem. Scand, 2<5, 585-595 (1972). 

Known plant toxins are 1. the homologous viscotoxins (Af, 4,840 46 amino acid residues of known sequence 3 disulfide bridges) from leaves and branches of the European mistletoe, which have hypotensive activity and cause a slowing of the heart beat 2. the toxalbumins Ricin (see) and abrin, which inhibit protein biosynthesis. 

Isolated polypeptides, viscotoxins II, III, and IVb, have been associated with cardio-toxicity but have also been found to exhibit cytotoxic activity against human tumor cells of the KB and HeLa lines in tissue culture. A peptide with a molecular weight of 5000 was found to be cytotoxic to Dalton s lymphoma ascites tumor cells in vitro in mice, without affecting normal lymphocjfies, indicating a cell-dependent specificity also cyctotoxic to Ehrlich ascites cells, both prophylacticaUy and after tumor development. Commercial mistletoe products have been used to treat various cancers in Europe with clinical success. A group of 50 cases of carcinomatous pleural effusions were treated with a topical preparation for an average of 3.3 application over 18 days exudation disappeared in 92% of the patients. In postoperative ovarian cancer patients, a mistletoe preparation statistically increased survival. ... 

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