Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mistletoe”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1999

Mistletoe lectin dissociates into catalytic and binding subunits before translocation across the membrane to the cytoplasm.

Hybridomas producing monoclonal antibodies (mAbs) against the mistletoe lectin A-chain (MLA) were obtained to investigate the intracellular routing and translocation of ribosome-inactivating proteins. Anti-MLA mAb MNA5 did not bind the holotoxin but interacted with isolated MLA. This epitope was not recognized upon MLA denaturation or conjugation of MLA with the ricin binding subunit (RTB). Furthermore, the mAbs did not appreciably react with a panel of MLA synthetic octapeptides linked to the surface of polyethylene pins. A study of the cytotoxicity of mistletoe lectin, ricin, and chimeric toxin MLA/RTB for the hybridomas revealed that interchain disulfide bond reduction and subunit dissociation are required for cytotoxic activity of mistletoe lectin.

Animals↗
PubMed1999

Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells.

Cytotoxic lectins (KML-C) were isolated from an extract of Korean mistletoe [Viscum album C. (coloratum)] by affinity chromatography on a hydrolysed Sepharose 4B column, and the chemical and biological properties of KML-C were examined, partly by comparing them with a lectin (EML-1) from European mistletoe[Viscum album L. (loranthaceae)]. The hemagglutinating activity of KML-C was inhibited by N-acetyl-D-galactosamine and D-galactose at the minimum concentrations of 6.3 and 12.5 microM/ml, respectively. Further biochemical analyses indicated that KML-C consists of four chains (Mr = 27.5, 30, 31 and 32.5 kDa) which, in some of the molecules, are disulfide-linked, and that the chains of KML-C are distributed over a broad range of isoelectric points (pI), 8.0 to 9.0, whereas the range for EML-1 is 6.6-7.0. A difference was also observed between the N-terminal sequences of KML-C and EML-1. The isolated lectins showed strong cytotoxicity against various human and murine tumor cells, and the cytotoxic activity of KML-C was higher than that of EML-1. Tumor cells treated with KML-C exhibited typical patterns of apoptotic cell death, such as apparent morphological changes and DNA fragmentation, and its apoptosis-inducing activity was blocked by addition of Zn2+, an inhibitor of Ca2+/Mg2+ -dependent endonucleases, in a dose-dependent manner. These results suggest that KML-C is a novel lectin related to the cytotoxicity of Korean mistletoe, and that its cytotoxic activity against tumor cells is due to apoptosis mediated by Ca2+/Mg2+ -dependent endonucleases.

Animals↗
PubMed2002

Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2.

The mucosal adjuvant properties of the three type 2 ribosome-inactivating proteins (RIPs) from the European mistletoe, Viscum album L., were investigated. Mistletoe lectins were compared with cholera toxin (CT) as adjuvants when delivered nasotracheally together with herpes simplex virus glycoprotein D2 (gD2). All three mistletoe lectins (MLI, MLII, MLIII) were potent mucosal adjuvants. Co-administration of MLI, MLII or MLIII with gD2 led to significantly higher levels of gD2-specific mucosal immunoglobulin A (IgA) and systemic immunoglobulin G (IgG) antibody than when the antigen was delivered alone. The levels of antibodies induced were similar to those generated in mice immunized with gD2 and the potent mucosal adjuvant CT. Administration of ML1 with gD2 enhanced the antigen-specific splenic T-cell proliferative response. Interleukin-5 (IL-5), but not interferon-gamma (IFN-gamma), was detected in supernatants from splenocytes stimulated in vitro with gD2. This indicates that MLI enhanced type 2 T-helper cell (Th2) responses to the bystander antigen, gD2. Analysis of the gD2- and lectin-specific IgG subclass titres in mice immunized with gD2 and MLI, MLII or MLIII revealed a high ratio of IgG1 : IgG2a, which is compatible with the selective induction of Th2-type immune responses.

Adjuvants, Immunologic↗
PubMed1999

Cloning of the mistletoe lectin gene and characterization of the recombinant A-chain.

Mistletoe lectin I (MLI) is the major active constituent of mistletoe extracts, which are widely used for adjuvant tumour therapy. The 66-kDa heterodimeric disulphide-linked glycoprotein is classified as type II ribosome-inactivating protein (RIP) due to the rRNA-cleaving enzyme activity of the A-subunit, also referred to as toxic entity. MLI and the close relative ricin both belong to the family of the two-chain plant type II RIP proteins. Isolation of the glycosylated proteins from plant material yield inhomogeneous material probably due to post-translational modifications. The aim of this study was to prepare pure and homogeneous protein as a prerequisite for structural and mechanistic studies in order to gain insight into the mode of action of this cytotoxic plant protein on tumour and immune cells. Of particular interest was to explain whether the differences in toxicity of ML and ricin are the result of variations of their enzymatic activities. By investigating the sequence homologies between the active sites of different RIPs we were able to deduce a set of primers which were suitable for specific amplification of the mistletoe lectin gene. Applying this PCR strategy the full-length 1923 nucleotide DNA sequence coding for the prepro-protein was obtained showing the existence of a single intron-free gene. In order to elucidate the molecular basis for the observed differences in cytotoxicity within the family of RIP the enzymatic A-subunit was expressed in a heterologous system. Expression of the A-chain in E. coli BL21/pT7 resulted in production of insoluble inclusion bodies constituting 20-30% of total protein. Refolding led to a pure and homogeneous protein species with an apparent molecular mass of 27 kDa and a pI value of 6.4. The ribosome-inactivating activity of the unglycosylated recombinant A-chain (IC50 20.5 pM) protein was in the same range as that of the glycosylated plant-derived ML A-chain (IC50 3.7 pM), which was very similar to that of ricin A-chain (IC50 4.9 pM). Thus, the higher cytotoxicity of ricin cannot be accountable for differences in the enzymatic activities of the type II RIP A-chains.

Amino Acid Sequence↗
PubMed2004

A new gene encoding the ribosome-inactivating protein from mistletoe extracts.

Extracts from mistletoe (Viscum album L.) contain three main toxic proteins--the lectins MLI (also known as viscumin), MLII and MLIII. A catalytic subunit of the mistletoe plant toxic lectin MLIII has been cloned and expressed in Escherichia coli cells. The structure and immunochemical properties of recombinant MLIII A-subunit were investigated using a panel of monoclonal antibodies against ML-toxins. Ribosome-inactivating activity of the recombinant MLIII A-subunit was determined in a cell-free system exhibiting inhibition of endogenous protein synthesis. The comparative analysis of nucleotide and deduced amino acid sequences of the cloned MLIII A and the native MLI A-subunits was performed, revealing the main differences in the primary structure of these proteins. Antigenicity analysis of the MLIII A-subunit has revealed a new epitope D179-E184 that is not present in viscumin. The role of toxic lectins with respect to the immunological properties of mistletoe extracts is discussed.

Base Sequence↗
PubMed2002

Detection of isolated mistletoe lectin chains in plant extracts.

New test systems which allow to detect with high sensitivity the presence of isolated subunits in mistletoe extracts subunits are proposed. Interaction of monoclonal antibodies MNA5 and mouse anti-MLA (mistletoe lectin I A-chain) immune serum with panel of synthetic octapeptides linked to the surface of polyethylene pins have been analyzed. Two main immunogenic epitopes in MLA, AETHL and DGVFNNP, were found. The second sequence can be part of the MNA5 antibody epitope as shown by antigenic prediction. Possible role of the isolated A- and B-chains of mistletoe lectins in pharmacological effects of plant extracts is discussed.

Animals↗
PubMed2004

Cloning and characterization of the genes encoding toxic lectins in mistletoe (Viscum album L).

Leaves of mistletoe (Viscum album L) contain three toxic lectins (type 2 ribosome-inactivating proteins) MLI, MLII, and MLIII, differing in molecular mass and carbohydrate specificity. Clones, containing sequences of three gene variants designated ml1p, ml2p, and ml3p, were obtained using PCR amplification from cDNA and from mistletoe genomic DNA. The quantitative ratio of the ml1p, ml2p, and ml3p genes in genomic DNA was found to be 1.5 : 1 : 4, respectively, whereas the ratio of their mRNA was 50 : 10 : 1. The quantitative prevalence of the ml1p transcript correlates well with the observation that MLI is quantitatively dominant over MLII and MLIII in the mistletoe extract. The sequences of the proteins encoded by the ml1p, ml2p, and ml3p genes are identical to MLI by 98, 88, and 77%, respectively. The similarity to MLI of the amino acid sequence encoded by the gene ml1p, the quantitative prevalent of its mRNA, as well as structural properties of the B-chain indicate that the gene, ml1p, corresponds to MLI. Western blot analysis of recombinant A-chains encoded by the three variants of mlp genes with the monoclonal antibody MNA4 having differential affinity to MLI, MLII and MLIII A-chains suggests that the ml2p and ml3p genes correspond to MLII and MLIII, respectively. Structural differences in the carbohydrate-binding sites of the B-subunits of ML1p, ML2p, and ML3p probably explain the difference in sugar specificity of MLI, MLII and MLIII.

Amino Acid Sequence↗
PubMed1981

Mistletoe hepatitis.

A 49-year-old woman presented with nausea, general malaise, and a dull ache in the right hypochondrium. Liver biopsy showed slight inflammatory-cell infiltration, and results of liver function tests suggested hepatitis. Hepatitis B surface antigen was not detected, and a cholecystogram was normal. Two years later she presented with similar symptoms, and both illnesses were found to have occurred after ingestion of a herbal remedy containing kelp, motherwort, skullcap, and mistletoe. A challenge test established this to be the cause of the illness. Mistletoe is the only constituent of the tablets known to contain any potential toxin and thus was probably the cause of the illness. Mistletoe is widely used in herbal remedies, whose ingestion may therefore cause hepatitis.

Chemical and Drug Induced Liver Injury↗
PubMedDate not supplied

Variable sensitivity of lymphoblastoid cells to apoptosis induced by Viscum album Qu FrF, a therapeutic preparation of mistletoe lectin.

BACKGROUND: Viscum album (VA) Qu FrF preparation consists of an aqueous extract of Viscum album, the European mistletoe. It has cytotoxic and immunomodulatory properties that support its usefulness in cancer therapy. However, only little information is available on the interaction between mistletoe lectin (ML) and the humoral compartment of the immune system. METHODS: Inhibition of proliferation of cells was performed by incorporation of (3)H-thymidine, and cell viability was assessed by the uptake of propidium iodide. Detection of Bcl-2 and related molecules was performed by SDS-PAGE followed by immunoblotting. RESULTS: We demonstrated that B lymphocyte lines are insensitive to VA Qu FrF-induced apoptosis. We showed, using Fas-sensitive and Fas-resistant cell lines, that VA Qu FrF-induced apoptosis is Fas independent. In both B and T lymphocytes, treatment of the cells with VA Qu FrF was associated with decreased levels of Bcl-2 and Bcl-X. CONCLUSIONS: Our results suggest that B lymphocyte depletion is not involved in the modulation of humoral immunity by ML. These observations should be of value in appropriate designing of cancer therapy using compounds containing mistletoe extracts.

Antibody Formation↗
PubMed2006

[Correlation of NK cell activity against autologous tumour cells and K562 cells with the clinical outcome during therapy with mistletoe extracts].

BACKGROUND: Suppression of NK cell activity is considered to be an unfavourable prognostic factor for tumour progression. There is proof that mistletoe extracts may increase NK cell activity. However, the inverse relation between an increase of NK cell activity and clinical progress of cancer has not been investigated. AIM AND DESIGN: The relation of NK cell activity and progress of cancer in patients under therapy with mistletoe extracts was examined in a prospective, monocentric, cohort study. At the same time the in vitro killing of K562 cells and autologous tumour cells was compared. PATIENTS AND METHODS: 40 patients with operable cancer of the breast or colon were included. The patients did not receive any immunologically relevant therapies except for mistletoe extracts. The absolute NK cell count in peripheral blood as well as the in vitro NK cell activity were monitored for up to 2 years and compared with clinical outcome as well as quality of life. RESULTS: The absolute NK cell count in peripheral blood increased within the observation period. Patients without progression had a significantly higher mean activity of NK cells against K562 cells than patients with progression. In the latter group, only stage IV patients showed reduced NK cell activity. The killing activity against autologous tumour cells was <5% in about 77.5% of the patients and could not be evaluated further. The NK cell activity against K562 cells was not related to the number of NK cells. CONCLUSIONS: We found a relation between NK cell activity and the progression of malignant disease. In further studies the causality of this relation has to be clarified. The establishment of NK cell activity against autologous tumour cells as a suitable parameter during follow-up was not successful.

Aged↗
PubMed1986

Studies on the standardization of mistletoe preparations.

The newly isolated phenylpropanoids syringin, syringenin-apiosylglucoside, eleutheroside E and the high molecular lectins and viscotoxins were selected for a standardization of mistletoe extracts and drug preparation. The phenylpropanoids found in all alcoholic and aqueous extracts were suitable for an HPLC fingerprint analysis, and for quantitative determination. The lectin content of the drug preparations was determined by single radial immunodiffusion. As shown by the isoelectric focussing method, Iscador and fermented mistletoe extracts contain only the mistletoe lectins ML II/III, whereas the proteins of the ML I complex are missing. For identification and quantitative determination of viscotoxins, an HPLC method was designed.

Chromatography, Affinity↗
PubMed1989

[Studies on pharmacological activity of the Japanese and European mistletoe].

The pharmacological actions such as analgesic effect, diuretic action, hypoglycemic activity and hypotensive action were studied on the methanol extract of the Japanese mistletoe and the European mistletoe. The both extracts showed the hypotensive action when administered intravenously to cat. The methanol extract of the Japanese mistletoe also showed a increase of K+ value in the urine when administered orally to rat.

Analgesics↗
PubMed2004

Abnoba-viscum (mistletoe extract) in metastatic colorectal carcinoma resistant to 5-fluorouracil and leucovorin-based chemotherapy.

A phase II trial was designed to determine whether mistletoe extract can induce objective tumor response in patients with metastatic colorectal cancer resistant to 5-fluorouracil and leucovorin (5FU/LCV)-based chemotherapy. Twenty-five patients (15 female, 10 male; median age 69 yr) were treated with commercially available mistletoe extract (Abnoba-viscum Quercus) given by three weekly subcutaneous injections with daily dose gradually increased from 0.15 to 15 mg plant extract. Treatment was discontinued if unacceptable toxicity developed or if the patient became bedridden. Median duration of treatment was 14 wk (range, 4-66 wk). Treatment was continued in 14 patients until they became bedridden, and 11 patients decided to discontinue the treatment after their illness progressed. Objective tumor response was not seen in any of the 25 patients (0%, 95% confidence interval 0-13.7%). Stable disease, lasting for a median of 2.5 mo (range, 1.5-7 mo), was noted in 21 (84%) patients. Median survival was 5.5 mo and symptomatic relief was reported by 10 (40%) patients. Toxicity was mild and included mainly local inflammatory reaction. In conclusion, mistletoe extract does not seem to be active in metastatic colorectal cancer resistant to 5FU/LCV in terms of objective tumor response.

Aged↗
PubMed1999

Insulin-secreting activity of the traditional antidiabetic plant Viscum album (mistletoe).

Viscum album (mistletoe) has been documented as a traditional treatment of diabetes. In acute 20-min tests, 1-10 mg/ml aqueous extract of mistletoe evoked a stepwise 1.1- to 12.2-fold stimulation of insulin secretion from clonal pancreatic B-cells. This effect was abolished by 0.5 mM diazoxide and prior exposure to extract did not alter subsequent stimulation of insulin secretion induced by 10 mM L-alanine, thereby negating a detrimental effect on cell viability. The insulin-releasing effect of mistletoe extract was unaltered by 16.7 mM glucose, l-alanine (10 mM), 3-isobutyl-1-methylxanthine (IBMX) (1 mM), or a depolarising concentration of KCl (25 mM). The ability of extract to enhance insulin secretion did not depend upon the use of heat during extract preparation and was not mediated by lectins. These results demonstrate the presence of insulin-releasing natural product(s) in Viscum album which may contribute to the reported antidiabetic property of the plant.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Potentiation of tumor necrosis factor-alpha-induced apoptosis by mistletoe lectin.

Mistletoe lectins (MLs) constitute the active principle in extract preparations from mistletoe, commonly used as immunomodulator in adjuvant tumor therapy. MLs, classified as type II ribosome inactivating proteins, inhibit protein synthesis. Inhibitors of protein synthesis may modify cancer cell response to tumor necrosis factor-alpha (TNF). In the present study, we have hypothesized that the anticancer efficacy of TNF may be potentiated by MLs. In deed, simultaneous treatment of human cervix carcinoma HeLa or breast carcinoma MCF-7 cells with MLs isolated from European or Korean mistletoe rendered them more sensitive to induction of apoptosis by TNF. The mechanism by which MLs amplify the effect of TNF may involve suppression of the survival protein synthesis.

Adjuvants, Immunologic↗
PubMed1999

Characterisation of immunological reactivity of patients with adverse effects during therapy with an aqueous mistletoe extract.

Drugs, which are effective are also bond to exert adverse effects. This is also true for mistletoe extracts. Extracts from European mistletoe (Viscum album, VAL) belong to the complementary therapeutic regimens and are used for adjuvant cancer therapy. This study was performed to characterise immunological reactivity of patients with adverse effects during treatment with an aqueous VAL extract (Helixor). VAL-stimulated proliferation and cytokine release of peripheral blood mononuclear cells (PBMC) and anti-mistletoe lectin (ML)-1 antibody production were investigated. 34 patients with proven adverse effects due to VAL therapy (group 1) and 9 patients with unproven relation (group 2) were studied and compared to 14 tumour patients treated with VAL for more than 2 years without side effects (TTP). VAL-stimulated proliferation of PBMC of group 1 was significantly enhanced as compared to group 2 patients and TTP. PBMC from patients with local manifestations proliferated significantly stronger than those from patients with systemic symptoms. Anti-ML-1 antibodies of the IgE type were produced in patients with proven adverse effects but not in patients without adverse effects. Production of Th1 and Th2 specific cytokines varied considerably, indicating that different mechanisms were involved in the induction of adverse effects. In conclusion, our study provide evidence that adverse effects towards VAL (Helixor) are seldom and are dominated by an application site reaction suggesting the involvement of delayed type hypersensitivity (DTH) reactions.

Adjuvants, Immunologic↗
PubMedDate not supplied

Anticancer activity of an aqueous mistletoe extract (AME) in syngeneic murine tumor models.

Mistletoe extracts have been used for decades for non-specific stimulation of the immune system in cancer therapy. Mistletoe lectins (ML) have been identified as the active principle with cytotoxic and immunomodulatory potencies. In the present in vivo experiments, the anticancer effects of an aqueous mistletoe extract (AME) were investigated in different subcutaneously growing syngeneic murine tumors such as Renca renal cell carcinoma, C8 colon 38 carcinoma, F9 testicular carcinoma, B16 melanoma and Lewis lung carcinoma. The animals used were immunocompetent mice of different strains (C57BL/6, BALB/c), depending on the type of tumor tested. After tumor transplantation, the mice were treated with AME at dose levels corresponding to 0, 0.3, 3, 30 or 300 ng ML/kg/d by the i.p. or s.c. route for a maximum of 4 consecutive weeks. The tumor volume was determined by serial caliper measurements and expressed relative to controls. Significant tumor growth inhibition was observed with the Renca , C8 colon 38 and F9 testicular carcinomas at 30 and 300 ng ML/kg/d. These findings were confirmed in independent repeat experiments. No inhibitory effects were seen with the Lewis lung carcinoma and B16 melanoma under the conditions described above. In conclusion, AME showed in vivo anticancer activity in different transplantable syngeneic murine tumor models following repeated parenteral treatment. In view of the low dose levels used, the effects are most likely due to the immunostimulatory rather than to the cytotoxic potencies of AME.

Animals↗
PubMed1992

Comparative lectinhistochemical studies on paraffin- and glycol methacrylate-embedded CNS tissue specimens from AIDS autopsies. Mistletoe lectin I (ML I) as cell-marker.

Brain tissue and spinal cord tissue from 12 patients who had died of AIDS was fixed in neutral formalin; then after the embedment of some of it in paraffin and some of it in glycol methacrylate, it was analyzed lectinhistochemically with mistletoe lectin I (ML I). Mistletoe lectin (ML I) is a reliable marker for microglia cells and macrophages and for special cell forms (polynuclear giant cells, so-called pericytes) belonging to this cell system. In both the embedding procedures used, the representation of the cells is very clear and subtly differentiated so that the preparations are very well suited to the study of AIDS-associated tissue damage in the CNS. Whereas the immunological macrophage markers (CD 68 markers) KPI, PG-M1 produce good results on paraffin-embedded material but are completely useless on material embedded in glycol methacrylate, the cells of the monocyte-macrophage system can be represented very well and reliably after being embedded in glycol methacrylate with mistletoe lectin I (ML I).

AIDS Dementia Complex↗