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 91 records · Page 5Linked to original sources

Neurophysiological effects of mistletoe (Viscum album L.) on isolated rat intestines.

Mistletoe (Viscum album L.) is well known as a medicine from ancient times and the earliest notes. Today it is used as a remedy. The aim of this research was to examine the effects of mistletoe extracts and their components on some neurophysiological parameters in rat intestines. The tonus and contractile responses of isolated intestinal segments (duodenum, ileum and distal colon) were analysed. The experiment was carried out in three groups. In the first group (control group) different concentrations of acetylcholine were added into the organ bath (10-50 nmol/L). In the second group, mistletoe extracts were added into the organ bath with increasing concentrations and in the third group, atropine, a non-selective muscarinic receptor antagonist, was added into the organ bath (concentration 10(-7) mol/L) and after atropine plant extracts were administered. The results obtained suggest that extracts from different parts of mistletoe have neurophysiological effects and change intestinal contractions. The results also suggest that the effects of mistletoe extracts on intestinal contractility act via cholinergic pathways, activating muscarinic receptors in the intestines. However, in order to establish the subtype of receptors, further investigations are necessary where selective antagonists of muscarinic cholinergic receptors should be used.

Animals↗

Occurrence of the lutein-epoxide cycle in mistletoes of the Loranthaceae and Viscaceae.

The lutein-epoxide cycle (Lx cycle) is an auxiliary xanthophyll cycle known to operate only in some higher-plant species. It occurs in parallel with the common violaxanthin cycle (V cycle) and involves the same epoxidation and de-epoxidation reactions as in the V cycle. In this study, the occurrence of the Lx cycle was investigated in the two major families of mistletoe, the Loranthaceae and the Viscaceae. In an attempt to find the limiting factor(s) for the occurrence of the Lx cycle, pigment profiles of mistletoes with and without the Lx cycle were compared. The availability of lutein as a substrate for the zeaxanthin epoxidase appeared not to be critical. This was supported by the absence of the Lx cycle in the transgenic Arabidopsis plant lutOE, in which synthesis of lutein was increased at the expense of V by overexpression of epsilon-cyclase, a key enzyme for lutein synthesis. Furthermore, analysis of pigment distribution within the mistletoe thylakoids excluded the possibility of different localizations for the Lx- and V-cycle pigments. From these findings, together with previous reports on the substrate specificity of the two enzymes in the V cycle, we propose that mutation to zeaxanthin epoxidase could have resulted in altered regulation and/or substrate specificity of the enzyme that gave rise to the parallel operation of two xanthophyll cycles in some plants. The distribution pattern of Lx in the mistletoe phylogeny inferred from 18S rRNA gene sequences also suggested that the occurrence of the Lx cycle is determined genetically. Possible molecular evolutionary processes that may have led to the operation of the Lx cycle in some mistletoes are discussed.

Carotenoids↗

Influx of double labelled glutamine into mistletoes (Viscum album) from the xylem sap of its host (Abies alba).

The flux of glutamine into the mistletoe Viscum album from the xylem sap of a coniferous host was analyzed. For this purpose, a perfusion system was used in which the xylem sap of the host was replaced by an artificial perfusion solution. With this system, flux rates into the mistletoe were determined in feeding experiments with the organic nitrogen source U(13)C/(15)N-Gln. At the end of the experiments the delta values of C and N were significantly depleted in the outflow compared to the percolation solution. Since this depletion was higher for C than for N, a combination of Gln uptake and simultaneous uploading of organic compounds in the host xylem can be assumed. Gln was strongly metabolized during its allocation in the mistletoe. As a consequence, the C skeleton of Gln was equally distributed between leaf and stem tissue, whereas N of Gln preferentially accumulated in the stem. Apparently, the C atoms of the Gln taken up are transported faster in the mistletoe to the sink tissues than the N atoms. It is concluded that C liberated from Gln is transported rapidly to different sink tissues, whereas N in the oversupplied mistletoes is transported slowly to sinks in the leaves.

Abies↗

Development and validation of an instrument to measure the effects of a mistletoe preparation on quality of life of cancer patients: the Life Quality Lectin-53 (LQL-53) Questionnaire.

Mistletoe preparations standardised to the content of mistletoe lectin are supposed to improve quality of life (QoL) in patients with cancer. To obtain a validated and sensitive research instrument, the Life Quality Lectin-53 (LQL-53) Questionnaire was developed in three phases: item generation via interviews with 42 patients, item selection by means of a study with 109 cancer patients, and psychometric testing. The LQL-53 includes 46 items assigned to the subscales 'General well-being', 'Emotional well-being', 'Vitality' 'Hope', 'Locus of control', Social relationships', and 'Physical complaints', plus seven items dealing with possible adverse effects of mistletoe treatment. Psychometric testing was carried out in a study with 112 patients with solid tumours who were treated with a mistletoe preparation standardised to mistletoe lectins for 12 weeks. Internal consistency (Cronbach's alpha) was between 0.72 and 0.94. Test-retest reliability was > or = r of 0.72. Subscales correlated highly with external criteria. Construct validity, as determined by Multitrait Scaling Analysis, resulted in an optimal assignment of items to subscales (scaling success) for four of the subscales. During the course of the therapy, significant improvement in QoL was found in all subscales. In two of the subscales, effect size was high (>0.80), and in five other subscales it varied between 0.53 and 0.78.

Adjuvants, Immunologic↗

Phosphoenolpyruvate carboxylase in mistletoe leaves: Regulation of gene expression, protein content, and covalent modification.

Seasonal changes in the activity of phosphoenolpyruvate carboxylase (PEPCase, EC 4.1.1.31), a key enzyme in the interaction of carbohydrate and nitrogen metabolism, were studied in leaves of the C3 semiparasitic mistletoe, Viscum album, growing on different host trees. Maximum extractable PEPCase activities were higher in leaves of mistletoes growing on Betula pendula and Alnus glutinosa hosts compared with those on the conifers, Abies alba and Larix decidua. Independent of host, maximum extractable PEPCase activities were high in spring and autumn while low in summer. Samples with higher PEPCase activities showed higher amounts of PEPCase protein and higher PEPCase mRNA levels. A curvilinear correlation between leaf total nitrogen content and the maximum extractable PEPCase activity as well as PEPCase mRNA level suggested that nitrogen might affect the activity of PEPCase of mistletoe by up-regulating gene expression. In addition to extractable activity, seasonal changes of the PEPCase activation state, the ratio of activities resulting from limited:non-limited assays, were found, which was correlated to the variation of malate content in leaves of mistletoe. ATP-dependent activation of PEPCase was characterized by an increase in I0.5(L-malate), indicating that PEPCase of leaves of mistletoes is probably regulated via phosphorylation.

Journal Article↗

Absence of tumor growth stimulation in a panel of 26 human tumor cell lines by mistletoe (Viscum album L.) extracts Iscador in vitro.

Mistletoe (Viscum album L.) extracts exhibit antitumor activity based on direct inhibition of tumor growth as well as modulation of immune response. Recent reports suggested potential stimulation of tumor growth at low doses of mistletoe extracts, particularly in hematological tumors and tumors responding to immunotherapy. Therefore, the direct effect of the three mistletoe extracts Iscador M Spezial, Iscador Qu Spezial and Iscador P on tumor growth was investigated in a panel of 26 human tumor cell lines in vitro using cellular proliferation assays. Antitumor activity of the three preparations at high concentrations was investigated in a panel of 12 cell lines. The results showed no evidence of stimulation of tumor growth by any of the three extracts, in particular the five tumor cell lines previously reported to be sensitive to direct mistletoe lectin stimulation. On the contrary, the lectin containing preparations Iscador M Spezial and Iscador Qu Spezial expressed a pronounced antitumor activity exhibiting a nearly identical antitumor profile compared to isolated mistletoe lectin 1.

Antineoplastic Agents, Phytogenic↗

Charting the isophasic endophyte of dwarf mistletoe Arceuthobium douglasii (Viscaceae) in host apical buds.

BACKGROUND AND AIMS: Dwarf mistletoes (Arceuthobium; Viscaceae) are highly specialized dioecious angiosperms parasitic on many gymnosperm hosts in the northern hemisphere. Several dwarf mistletoe species are capable of inducing an unusual form of isophasic infection in which the internal (endophytic) system proliferates even into the apical buds of its hosts. Studies of the internal endophytic system have, for the most part, focused on the parasite within secondary host tissues. The present anatomical and ultrastructural study characterizes the growth pattern of the isophasic endophytic system of Arceuthobium douglasii within the dormant apical buds of Pseudotsuga menziesii. METHODS: Semi-thin serial sections from dwarf mistletoe-infected host apical buds were mounted, stained and micrographed. Graphic files were created from the serial micrographs and these files were stacked. These stacked files were utilized to describe the pattern of growth of the endophyte within the host tissue. The interface between cells of the mistletoe and host was also examined at the ultrastructural level by transmission electron microscopy. KEY RESULTS: By utilizing a novel technique of superimposed graphics, the current study reveals an organized pattern of mistletoe distribution that penetrates further into host tissues than previously known. A consistent pattern of growth occurring even into the preformed leaves of the host is documented. CONCLUSIONS: The apparently non-intrusive growth of the parasite appears to be developmentally synchronized with that of the host. No symplastic connections were observed in the ultrastructural examination of the parasite/host interface within the apical buds of Pseudotsuga menziesii parasitized by A. douglasii or of Pinus contorta parasitized by A. americanum.

Cell Nucleus↗

Impact of eastern dwarf mistletoe (Arceuthobium pusillum) infection on the needles of red spruce (Picea rubens) and white spruce (Picea glauca): oxygen exchange, morphology and composition.

Eastern dwarf mistletoe (Arceuthobium pusillum Peck) is a hemiparasitic angiosperm that infects white spruce (Picea glauca (Moench) Voss) and red spruce (P. rubens Sarg.) in northeastern North America. The effects of mistletoe infection differ substantially between white and red spruce, with white spruce suffering greater infection-induced mortality. In the present study, we sought to determine the role that species-specific differences in needle-scale responses to parasitism may play in the observed differences in the effect of infection on host tree health. Based on the measurements made, the most apparent effect of parasitism was a reduction in needle size distal to infections. The magnitude of this reduction was greater in white spruce than in red spruce. Eastern dwarf mistletoe was a sink for host photosynthate in red spruce and white spruce; however, there were no adjustments in needle photosynthetic capacities in either host to accommodate the added sink demands of the parasite. Needle total nonstructural carbohydrate concentrations (TNC) were also unaltered by infection. Red spruce needles had higher TNC concentrations despite having lower overall photosynthetic capacities, suggesting that red spruce may be more sink limited and therefore better able to satisfy the added sink demands of parasitic infection. However, if carbon availability limits the growth of the mistletoe, one may expect that the extent of the parasitic infection would be greater in red spruce. Yet in the field, the extent of infection is generally greater in white spruce. Taken together, these results suggest that dwarf mistletoe may not substantially perturb the carbon balance of either host spruce species and that species-specific differences in needle-scale responses to the parasite cannot explain the contrasting effects of infection on white spruce and red spruce.

Carbohydrates↗

Adjuvant intravesical treatment of superficial bladder cancer with a standardized mistletoe extract.

PURPOSE: Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin (BCG) for noninvasive superficial bladder cancer has been shown to decrease tumor recurrence significantly. However, serious local and systemic side effects of this treatment have promoted the use of other immunoactive substances, which to date have failed to show efficacy equal to that of BCG immunotherapy. MATERIALS AND METHODS: In the current phase I/II clinical trial an aqueous mistletoe extract standardized to mistletoe lectin was administered intravesically to 30 patients with superficial urothelial bladder carcinoma. About 4 weeks after transurethral resection each patient received 6 instillations at weekly intervals of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml, which was retained in the bladder for 2 hours. Three patients per group received a dose, which was then doubled in the next group. Clinical followup consisted of examinations with cystoscopy, cytology and random biopsies. To detect cytokines and tumor necrosis factor-p75 receptor venous blood and urine samples were taken before instillation, and 2, 6 and 24 hours thereafter. RESULTS: The tolerability of intravesically administered mistletoe extract was good at all applied concentrations. None of the patients had local or systemic side effects according to WHO classification 1-4. Within the 12-month observation time study patients with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33%, comparable to that in a local historical control group of patients with equal stage and grade who were treated with adjuvant BCG. Comparison of urine cytokine levels before instillation, and 2, 6 and 24 hours thereafter brought about no significant alterations in all measured cytokines. CONCLUSIONS: From these results it is concluded that standardized mistletoe extract could be a potential alternative adjuvant therapy for superficial bladder cancer. Nevertheless, the optimal intravesical treatment regimen has yet to be defined.

Administration, Intravesical↗

Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial.

PURPOSE: The indication for topic chemotherapy or immunotherapy for well differentiated, noninvasive superficial bladder cancer remains controversial. Side effects of these treatments promoted use of unconventional therapies with cytokines, immunomodulators and mistletoe extracts. However, there are no controlled clinical data available on the efficacy of these extracts for bladder cancer. We evaluate the influence of subcutaneously applicated mistletoe lectin on bladder tumor recurrence after transurethral resection. MATERIALS AND METHODS: The study consists of 45 patients with pTa G1-2 bladder cancer treated with transurethral resection during a 3-year period. Median patient age was 65 years and 33 patients were male. The study cohort was randomly divided into a treatment group receiving adjuvant therapy with mistletoe lectin and a control group receiving no additional treatment. Patients in the treatment group received mistletoe lectin according to schedule 2 weeks after transurethral resection. Clinical followup was assessed 3, 6, 9, 12 and 18 months after the initial resection, and included uretherocystoscopy. RESULTS: Both study arms comprised similar patients with regard to total number of previous tumors (mean 2.6 versus 2.9), number of primary lesions (14 versus 12) and number of recurrent tumors (8 versus 11). After followup of 18 months the recurrence-free interval in both study arms was similar (p = 0.76) and the total number of recurrences comparable (p = 0.48). CONCLUSIONS: Subcutaneous use of mistletoe lectin as adjuvant treatment after transurethral resection does not seem to affect the time to first recurrence, total number of recurrences or recurrence-free outcome.

Aged↗

Cellular immunomodulation and safety of standardized aqueous mistletoe extract PS76A2 in tumor patients treated for 48 weeks.

Non-selected tumor patients (n=12) with various solid carcinomas were treated continuously twice weekly over 48 weeks with the aqueous mistletoe extract PS76A2, standardized to active mistletoe lectin. The preparation was applied subcutaneously at a concentration of 15 ng mistletoe lectin per 0.5 ml. Cellular immune response and safety were determined at various times during and after the therapy. In the course of treatment, virtually all the investigated immunoparameters were raised compared to the baseline values at the start of treatment. The statistically significant rises in the cell count of total lymphocytes, monocytes and natural killer (NK) cells was noteworthy. The differences in comparison with the baseline values at the various measuring times during treatment were up to 35%. In the first weeks of treatment at least, the raised cell count of NK cells correlated with the significantly increased cytotoxic activity versus tumor cells ex vivo. The NK factor (product of NK cells and ex vivo activity) was determined to assess the total NK activity more accurately, which rose up to 50% compared to the baseline value. Other lymphatic subpopulations, for instance CD3+, CD8+, CD3+CD4+ and CD3+CD8+ cells, also revealed distinct rises in cell count in the course of treatment. Within 6 weeks after completion of treatment, the overall values dropped again; but for a series of immunoparameters--in particular for the NK cells--they were still raised in comparison to the baseline values. The extensive laboratory diagnostics (haematology, clinical chemistry) showed that treatment with the standardized mistletoe extract PS76A2 was well tolerated by all patients. In single cases, local reactions at the injection sites were of a minor nature and reversible within two days. Summarizing, it can be stated that the standardized mistletoe extract PS76A2 significantly improved the immune status of tumor patients and was administered safely over a long period.

Adjuvants, Immunologic↗

Effects of mistletoe lectin I and ionizing radiation on the glucose and thymidine uptake in tumour cells in vitro.

The increased uptake of hexose by mammalian cells is considered to be a general response to stress. Nowadays, mistletoe lectin separated from the extracts of the European mistletoe (Viscum album L.) is often used in adjuvant cancer therapy. The present work studies the effect of the lectin on unirradiated and x-irradiated tumour cells. The response of cultured human lung carcinoma cells (Calu-1) was followed by radioactive glucose uptake as well as by tritiated thymidine incorporation. The cells were maintained either in a complete or a so-called restrictive medium. Slight metabolic changes were found in the restrictive medium but not in the complete one. Mistletoe lectin I at a very low concentration (0.001 ng/mL) increased the glucose uptake and thymidine incorporation. Ionizing radiation (1 Gy) did not influence the hexose uptake but it enhanced the incorporation of thymidine. It seems that the actions of two different factors (mistletoe lectin I and radiation) proved to be rather provoking stress effects for the tumour cells as detected in the restrictive medium.

Combined Modality Therapy↗

Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response.

Aqueous extracts from leaves of the European mistletoe (Viscum album L.) are postulated to exert an anticancer efficacy by cytotoxic and/or immunological mechanisms of action. Although popular as an unconventional therapy modality, no controlled randomized clinical trials are available, reliably documenting a clinically beneficial antineoplastic potential of the various commercial mistletoe preparations. Since previous investigations have focused on the purified galactoside-specific lectin (Viscum album L. agglutinin, VAA) as major biological response modifier in the low-dose range, the objective of the present experimental study was to examine its effect on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced carcinogenesis in the urinary bladder of rats, a suitable animal model for human disease. The carcinogen was fed by gavage in three fractionated low doses (150 mg/kg body weight each) to obtain low-grade and low-stage transitional cell carcinomas. From the onset of the experiment VAA was injected subcutaneously twice a week (1 ng/kg body weight) continuously for either 6 or 15 months. Following an experimental period of 6 months the incidence of bladder carcinomas was 10.2% in rats given exclusively BBN and 6.7% in those additionally treated with VAA. After an experimental time of 15 months 25.8% of the rats fed BBN only and 19.7% of the animals additionally receiving VAA had developed urothelial carcinomas. The differences of the tumor incidences did not reach the level of statistical significance, neither after an experimental duration of 6 (P = 0.88) nor of 15 months (P = 0.71). A difference was found in the size of the transitional cell carcinomas. They proved to be significantly larger (P = 0.02) in the rats additionally treated with VAA for 15 months (mean maximum diameter: 3.31 mm) than in those without lectin treatment (mean maximum diameter: 1.88 mm). Quantitative immunocytochemistry analyzing a panel of immune cells yielded no evidence for the ability of the lectin to provoke a substantial, biologically relevant local cellular immune response in the wall of tumor-free and tumor-bearing bladders. From the current experiment it is obvious that galactoside-specific mistletoe lectin failed to protect against, inhibit, delay or reduce development of chemically induced urothelial carcinomas of the urinary bladder even after long-term administration in the clinically recommended schedule. It seems highly unlikely that adjuvant treatment with mistletoe extracts or VAA might favorably influence bladder cancer in patients by immunological effector mechanisms.

Animals↗

Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosourea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration.

Extracts from mistletoe (Viscum album L.) are assumed to exert an antineoplastic activity through their toxicity at high doses or by immunomodulation by nanogram quantities of a lectin. They are used as an unconventional therapy modality in the management of a wide range of cancer diseases, although no anticancer potential has yet been demonstrated. This prompted us to study the effect of galactoside-specific lectin (VAA)--a major protein constituent of mistletoe with immunomodulatory properties--on chemically induced tumor development in the urinary bladder of rats and on the local cellular immune response after long-term administration. To induce urothelial neoplasms N-methyl-N-nitrosourea (MNU) was administered in a single intravesical dose (7.5 mg/kg body weight). Highly purified VAA was given subcutaneously at its immunomodulatory dose (1 ng/kg body weight) twice a week over the total experimental period of 15 months. The incidences of epithelial bladder tumors were 25.0% following administration of MNU alone and 22.9% in the rats additionally receiving VAA, which proved not to be significantly different (P = 0.81). Quantitative immunohistochemistry analyzing a panel of immune cell types, including T lymphocytes, T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8), T cells positive for interleukin-2 receptor (CD25), B lymphocytes and plasma cells, macrophages, natural killer cells, granulocytes and all leukocytes expressing the leukocyte common antigen (CD45), yielded no evidence for the ability of VAA to stimulate a substantial cellular immunological reaction in the wall of the normal urinary bladder or during urothelial carcinogenesis. In conclusion, the current experimental findings provide no support at all that the galactoside-specific mistletoe lectin is capable of inhibiting chemically induced bladder carcinogenesis and triggering a local cellular immune response after prolonged application. It thus seems highly improbable that commercial mistletoe preparations or VAA will be effective in the management of human bladder cancer by a cell-mediated immunological mechanism.

Adjuvants, Immunologic↗

Immunologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo.

Even though mistletoe extracts have been in clinical use for centuries their exact mode of action is still unknown. Currently, the application scheme for registered preparations is a dose-escalating scheme to thus reduce side effects. In this study, healthy controls and patients were evaluated for their immunologic response to treatment with a standardized mistletoe extract (Iscador). It shows a strong effect as adjuvant that induces TNF-alpha and IL-12, which was partly mediated via CD14. Desensitization of the TNF-alpha response could be shown after repeated application in vitro and in vivo. Furthermore, Iscador induces a specific lymphocyte sensitization upon multiple injections and production of IgG1- and IgG3 -mistletoe antibodies. Remarkably, a systemic bystander effect (heterologous immunity against other recall antigens) was observed after long-term treatment. In conclusion, dose-escalation reduces the monocyte-related clinical side effects. A T-lymphocyte sensitization stimulates mainly a specific Th1 response. The most interesting clinical long-term effect is the bystander stimulation of various memory T cells that might mediate in vivo antitumor and antiinfectious T-cell response under mistletoe-extract immunization.

Adjuvants, Immunologic↗

Isolation and partial characterization of a small chitin-binding lectin from mistletoe (Viscum album).

A novel lectin, called VisalbCBA, was isolated from European mistletoe (Viscum album). This lectin differs completely from the classical galactose/N-acetylgalactosamine-binding mistletoe lectins MLI, MLII and MLIII. Biochemical analyses indicated that VisalbCBA is a dimeric protein composed of two identical subunits of approx. 10 kDa. VisalbCBA exhibits specificity towards oligomers of N-acetylglucosamine and shows sequence homology to the previously isolated chitin-binding plant proteins. Although VisalbCBA is less toxic than the other mistletoe lectins, it definitely exhibits cytotoxic properties. The possible involvement of VisalbCBA in the biological and therapeutic effects of mistletoe is discussed.

Amino Acid Sequence↗

A mistletoe lectin (ML-1)-containing diet reduces the viability of a murine non-Hodgkin lymphoma tumor.

In this study we show that the characteristics of non-Hodgkin lymphoma (NHL) tumors in female Naval Medical Research Institute (NMRI, USA) mice fed mistletoe lectin (ML)-containing diets were different from those in mice fed control diet. The non-Hodgkin lymphoma tumor was originally established from a spontaneous tumor which developed in the inguinal region of a male mouse. Mice (five animals per group) were fed a lactalbumin (LA)-based control diet or a diet which provided up to 10 mg lectin per day. At the highest daily intake (10 mg lectin) the degree of mitotic activity in tumors was reduced by 75% and the nuclear area had diminished by 21%. The overall level of lymphocyte infiltration (CD3 positive cells) in tumors from mistletoe lectin fed mice was increased by a factor of two. Other morphological studies showed a high incidence of apoptotic bodies in non-Hodgkin lymphoma tumors obtained from mice fed mistletoe lectin diets. The feeding of such diets thus produced several identifiable changes in the morphology of non-Hodgkin lymphoma tumors. These were consistent with the observed reduction in tumor mass. In 4/15 mice fed a mistletoe lectin diet for 11 days there was no longer evidence of viable tumor. The results show that this lectin exerts powerful anti-tumor effects when provided by the oral route.

Animals↗

Involvement of hydrogen peroxide in mistletoe lectin-II-induced apoptosis of myeloleukemic U937 cells.

Mistletoe lectin-II, a major component of Korean mistletoe (Viscum album var. coloratum) induces apoptotic death in cancer cells. In this study, we demonstrated that lectin-II induced the generation of pro-oxidants and thus resulted in the apoptotic death of human myeloleukemic U937 cells. We observed that lectin-II-induced apoptotic death was inhibited by antioxidants including reduced glutathione (GSH), N-acetylcysteine (NAC), ebselen, mnTBP, catalase and pyrrolidine dithiocarbamate (PDTC). GSH and NAC also abolished the apoptotic DNA ladder pattern fragmentation of U937 cells after lectin-II stimulation. Obviously, lectin-II treatment of cells resulted in a remarkable generation of intracellular hydrogen peroxide (H2O2) as an early event, which was monitored fluorimetrically using scopoletin-horse radish peroxidase (HRP) assay and peroxide-sensitive fluorescent probe, DCF-DA. In addition, antioxidants inhibited the activation of c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) as well as cytosolic release of cytochrome c by mistletoe lectin-II. Moreover, lectin-II-induced activation of caspase-9 and 3-like protease and cleavage of poly(ADP-ribose) polymerase (PARP) were inhibited by pretreatment of cells with thiol antioxidants, GSH and NAC. Taken together, these results suggest that Korean mistletoe lectin-II is a strong inducer of pro-oxidant generation such as H2O2, which mediates the JNK/SAPK activation, cytochrome c release, activation of caspase-9 and caspase 3-like protease, and PARP cleavage in human myeloleukemic U937 cells.

Antioxidants↗