DNC News

 

Culture Wars, Mistletoe, Kissing and Cancer

December 15, 2006

Jacob Schor, ND

 

"Here we must mention the reverence felt for this plant by the Gauls. The Druids -- for thusly are their priests named - hold nothing more sacred than the mistletoe and the tree that bears it, as long as that tree be an oak.... Mistletoe is very rarely encountered; but when they do find some, they gather it, in a solemn ritual....

"After preparing for a sacrifice and a feast under the oak, they hail the mistletoe as a cure-all and bring two white bulls there, whose horns have never been bound before. A priest dressed in a white robe climbs the oak and with a golden sickle cuts the mistletoe, which is caught in a white cloak. Then they sacrifice the victims, begging the god, who gave them the mistletoe as a gift, to make it propitious for them. They believe that a potion prepared from mistletoe will make sterile animals fertile, and that the plant is an antidote for any poison. Such is the supernatural power with which peoples often invest even the most trifling things"

Pliny the Elder (23-79 AD)

 

 

As I read through this year's research on Viscum alba, or what we commonly call, mistletoe, I am reminded of that culture war debate over whether commercial establishments should wish shoppers a Merry Christmas or Happy Holidays. No matter what welcoming Wal-Mart uses to greet its customers, this is the season of mistletoe and holy. That these plants still plays any role in our holiday celebrations reminds me how deeply rooted our winter celebrations are in Druidic and Norse culture, for these plants played vital roles in both.

 

Mistletoe, like holly, is winter fruiting and an evergreen; the leaves of both plants stay green as they produce berries in the dead of winter. It is easy to understand why earlier cultures revered both plants as symbols of immortality and rebirth. When every thing else in the world appeared to have died, these plants are full of life. For people deeply connected with the natural world, these traits certainly stood out.

 

My goal in writing this article is to review the recent research on Viscum alba and its potential role in treating cancer but first, a digression is required to at least acknowledge mistletoe's historic and religious significance. This is necessary in part to help understand some of the current fascination.

 

For a moment, imagine an earlier world without our current understanding of the solar system, or the understanding of winter and spring solstices; a world in which there was less certainty that longer days would return. Then imagine living in the northern latitudes where the days at this time of year are even shorter than here in Denver . It takes little imagination to see that these shortening days would be worrisome.

 

Another consideration that we easily forget is that reliable means of food preservation are a recent development. Prior to refrigeration, freezing, and safe grain storage, winter was a mixed blessing as far as eating. Food stores of grain and meat were in good supply in early winter following fall harvests and the fall butchering. It was often a race to consume this fall abundance before it spoiled and was inedible. Putting on a few extra pounds during these weeks is a tradition that goes back millennia.

 

In parts of this earlier world, the fifth day following the new moon that follows the winter solstice, was the day on which Druid priests harvested mistletoe. With ritual ceremony, they cut the mistletoe down from oak trees using a golden sickle while their attendants caught the branches in their robes before the mistletoe touched the ground.

 

Mistletoe is a parasitic plant that lives on trees. Although the leaves contain some chlorophyll, a mistletoe plant can't make enough food to feed itself; it obtains most of its nutrition from the host tree. Birds eat mistletoe seeds and then carry them from tree to tree. The seeds will not sprout until the berries are digested. After birds digest the berries, they excrete the seeds in a super sticky mass which sticks to whatever it lands on. This sticky bird crap seed mass of mistletoe, which again is widely known as Viscum, gives rise to the word, viscous. If that viscous Viscum seed excrement lands on a tree, the seed sprouts, sending roots through the bark and into the tree to draw water and nourishment. Mistletoe spends its entire life cycle never touching the earth, an attribute that gave it early mystic significance.

 

Wal-Mart may supplant holiday wishes with Christian greetings, but no one is about to forget that you are allowed to kiss anyone you find standing beneath mistletoe. The most common explanation I read to explain this kissing tradition goes back to Norse story of Frigga and Balder.

 

Theirs is a story of overprotective motherhood. Frigga, the goddess of love and beauty and probably hovering motherhood, did her best for Balder, her favorite son. She went all through the world and secured promises from all beings and things that sprang from the four elements--fire, water, air, and earth, that they would not hurt her son Balder. The Achilles heel of this plan of course was mistletoe. Mistletoe it was thought came from nowhere. It sprang from none of the four elements. If it sprang from anything, it sprang from bird poop but at the time of the story, this route of seed transmission was overlooked. The story goes that Loki, the sly evil spirit of Norse mythology, made an arrow of mistletoe and tricked Balder's blind brother Hoder into shootiing Balder through the heart with it.

 

Frigga does a lot of weeping in the story and in the cold winter, her tears turn into the white berries of mistletoe. The berries of this immortal plant wake Balder back to life and the plant becomes a symbol of love. Et cetera.

 

There is another more obvious explanation for this kissing under mistletoe tradition. Mistletoe is an abortifacient; it can both prevent pregnancy or prevent a pregnancy from going to term. It no doubt acted as an early but effective form of birth control when consumed. And mistletoe was apparently consumed in adequate quantities during the early Druidic seasonal feasts. People figured out that in the ‘mistletoe season' they could get away with promiscuous behavior without the typical expected consequence. We preserve this understanding from early Druidic culture that mistletoe allows promiscuity without repercussion.

 

All this prehistory and pagan tradition is needed to wade through the current mistletoe and cancer business. I fear that some of the enthusiasm for mistletoe and some of the aversion to its use both stem from cultural views that stem from this earlier history.

 

The modern use of mistletoe for cancer treatment is credited to Rudolf Steiner. Steiner (1861-1925) was the Austrian philosopher behind something called anthroposophy, something Wikipedia describes as, “a movement based on the notion that there is a spiritual world accessible to pure thought through a path of self-development.” Whatever exactly that means. In modern terms, we might want to write this off as just another cult but that would do Steiner and his followers, of which there are still many, a great injustice. Steiner came up with many practical applications of his philosophy and worldview that are still with us, including biodynamic agriculture, anthroposophical medicine, eurythmy and the one we are probably the most familiar with, Waldorf Education.

Rudolf Steiner 1889

 

Steiner's followers who practice Anthroposophical medicine developed and favor a product called Iscador. It is a fermented preparation of mistletoe grown on oak tress and marketed by Weleda. The fermented mistletoe is combined with homeopathic doses of various metals including silver, copper and mercury. Keep this in mind as some of the modern use of mistletoe has certainly been influenced by the belief among Steiner's followers that it works rather than clinical experience or scientific data alone.

Iscador is well accepted in Germany , Switzerland and Northern Europe as an approved cancer treatment. Today, mistletoe extracts are the most frequently prescribed unconventional cancer therapies in Germany and in some other European countries. In Europe , approximately 60 to 70 percent of cancer patients use mistletoe. Whether or not mistletoe is actually effective for treating cancer has been debated for years. A number of positive studies appeared in the German medical literature in the late 1980's and early 1990s.

Yet while well accepted in Europe , mistletoe is uncommon in the United States . The American Cancer Society has long condemned it and for years warned against people against using it. Their website is a reliable source of negative research on Iscador.

The most important of these negative studies is from Eggermont and his colleagues, who compared Iscador to interferon in treating melanoma. Between 1988 and 1996, the European Organization for Research and Treatment of Cancer Melanoma Group performed a prospective, randomized phase III trial that compared the effects of several types of interferon or Iscador against an untreated control group. High-risk patients were randomized and followed until their first progression or death. In the end, there was no apparent difference in either disease free survival or overall survival in any of the interferon groups or the Iscador patients over the control group. In other words, taking Iscador didn't do these patients any good. [i] Of course, one has to keep this in perspective. Pretty much nothing works well for treating this form of cancer. Iscador was no miracle cure but this should not be a great surprise.

There are reports in the literature of cases that appear to respond to Iscador. A 1989 article in Thorax describes a case of small cell lung cancer that got better with Iscador treatment. [ii] Still for the most part, we don't hear much about Iscador inn the United States , except for a small flurry of interest when Suzanne Summers admitted she was using it.

This last year though was different because a number of interesting studies on Iscador were published. In January, an Israeli group reported reviewing 15 different prospective studies on Iscador and finding that most reported positive results. [iii] The same researchers published a paper in Anticancer Research in February describing their success at using Iscador to treat fluid build up in the abdomen of patients with advanced cancer. [iv]

In March, a Russian study reported that Iscador improved quality of life measurements of patients undergoing chemotherapy and radiation for breast cancer. [v] In June, French researchers published a paper comparing Iscador (made from oak mistletoe) against mistletoe extracts prepared from apple or pine grown mistletoes. They suggested that, at least in part, the effect of mistletoe involves mediation of nitric oxide production. [vi]

June was the big month. One June paper compared the genetic characteristics of various breast cancer cell lines and their response to various mistletoe extracts. [vii] Another June study, described the characteristics of cell death caused by mistletoe in multiple myeloma and lymphoma. The faster growing the tumor cells were, the more effective mistletoe was at killing them. [viii] Still another June study comparing the effect of mistletoe on various types of cancer cells, found that colon and rectal cancer cells had the least response. [ix]

In July a paper published in the International Journal of Immunology described the effects of Iscador on immune function and theorized how these changes could fight cancer. [x]

In September, Anticancer Research published a paper authored by Swiss doctors comparing various mistletoe extracts to see which was most effective against pediatric brain tumor cells. [xi]

Despite the popularity of Iscador in Europe , it is still rare to see it used in the United States , even among alternative providers. The American Cancer Society opposes its use and routinely posts warnings that it is ineffective or even dangerous on their website. The intensity of this opposition is what reminded me of the debate on seasonal greetings. People have strong opinions. Much of the heat in this debate on the merits of mistletoe may stem back to its association with pagan religions and with Steiner's ‘philosophical cult.' If this is indeed the case, it is no wonder that it is difficult to sort through the pros and cons. Both the proponents and the opponents to its use may be swayed by unacknowledged beliefs unrelated to its potential for therapeutic benefit. Let us hope that time and unbiased researchers will soon sort this out.

In the meantime, this is still the season to hang mistletoe and the practice appears well accepted at Christmas parties regardless of its origins. Pagan, Druid, or Christian, few people object to this custom or the traditional practices that occur when standing beneath it.

http://www.apsnet.org/online/feature/mistletoe/image/tainter1sm.jpg

 

 

 

[i] Eur J Cancer. 2004 Feb;40(3):390-402.

Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis.

•  Kleeberg UR ,

•  Suciu S ,

•  Brocker EB ,

•  Ruiter DJ ,

•  Chartier C ,

•  Lienard D ,

•  Marsden J ,

•  Schadendorf D ,

•  Eggermont AM ;

•  EORTC Melanoma Group in cooperation with the German Cancer Society (DKG) .

Haematologisch-Onkologische Praxis Altona (HOPA), Max-Brauer-Allee 52, D-22765 Hamburg , Germany . urkleeberg@hopa-hamburg.de

Between 1988 and 1996, the European Organisation for Research and Treatment of Cancer Melanoma Group (EORTC-MG) performed a prospective, randomised phase III adjuvant trial to evaluate the efficacy and toxicity of low dose recombinant interferon-alpha 2 b (rIFN-alpha2b) (1 MU) or recombinant interferon gamma (rIFN-gamma), (0.2 mg) both given subcutaneously (s.c.), every other day (qod), for 12 months in comparison with an untreated control group. The German Cancer Society (DKG) added a fourth arm with Iscador M, a popular mistletoe extract. High-risk stage II patients (thickness >3 mm) and stage III patients (positive lymph nodes) without distant metastasis were randomised and followed until their first progression or death. An intention-to-treat analysis was performed. From 1988 to 1996, a total of 830 patients were randomised: 423 in the three-arm EORTC 18871 trial and 407 patients in the four-arm DKG 80-1 trial. The median follow-up was 8.2 years and a total of 537 relapses and 475 deaths were reported. At 8 years, the disease-free interval (DFI) rate was 32.4% and the overall survival (OS) rate was 40.0%. In terms of the DFI, the hazard ratio estimates (95% Confidence Intervals (CI)) were: 1.04 (0.84, 1.30) for the comparison of rIFN-alpha2b versus control, 0.96 (0.77, 1.20) for rIFN-gamma versus control, and 1.32 (0.93, 1.87) for Iscador M versus control. In terms of OS, the corresponding estimates (95% CI) for the 3 treatment comparisons were: for IFN-alpha2b 0.96 (0.76, 1.21), for rIFN-gamma 0.87 (0.69, 1.10) and for Iscador M 1.21 (0.84, 1.75), respectively. The results show no clinical benefit for adjuvant treatment with low dose rIFN-alpha2b or rIFN-gamma or with Iscador M in high-risk melanoma patients.

PMID: 14746858 [PubMed - indexed for MEDLINE]

 

[ii] Thorax. 1989 Dec;44(12):1047-8.

Apparent response of small cell lung cancer to an extract of mistletoe and homoeopathic treatment.

 

* Bradley GW,

* Clover A.

 

William Harvey Hospital , Ashford , Kent .

 

A patient with small cell lung carcinoma was treated initially with extracts of mistletoe and homoeopathic treatment and appeared to respond. Subsequently radiotherapy was given and the patient lived for five years seven months, which is much longer than is usual with this type of tumour.

 

PMID: 2559483 [PubMed - indexed for MEDLINE]

 

[iii] Harefuah. 2006 Jan;145(1):42-6, 77.

[Mistletoe (Viscum album) preparations: an optional drug for cancer patients?]

[Article in Hebrew]

•  Bar-Sela G ,

•  Gershony A ,

•  Haim N .

Department of Oncology, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa , Israel . g_barsela@rambam.health.gov.il

Extracts and preparations from the parasitic plant mistletoe (Viscum album L.) have been used in the treatment of cancer for decades. Mistletoe treatment for cancer was introduced in 1920 by Steiner and Wegman, founders of the Anthroposophical medical method. Today, mistletoe extracts are the most frequently prescribed unconventional cancer therapies in Germany , as in some other European countries. Full clinical data about the efficacy of the mistletoe preparations is still missing. The preparations are usually given as subcutaneous injections, but other routes of administration are also used. Numerous preclinical and in-vitro studies have reported immunostimulatory, cytotoxic and proapoptotic effects. More than 15 prospective clinical trials using mistletoe extracts in patients with different malignancies have been reported. In most of these studies the authors reported that mistletoe extracts had therapeutic benefit in terms of response rate, overall survival, quality of life and reduction in side-effects of the oncological treatment. Unfortunately, almost all of these reported studies had at least one major weakness that questioned their reliability. Side effects of the different mistletoe preparation used in human studies are generally minimal and non-life threatening. In the current review recent studies, including two phase II studies from our center, are included. In the future, data that will be obtained from good quality studies might facilitate reaching firm conclusions regarding the therapeutic benefit of mistletoe preparation for oncological treatment.

PMID: 16450726 [PubMed - indexed for MEDLINE]

 

 

[iv]

Anticancer Res. 2006 Jan-Feb;26(1B):709-13.

Reducing malignant ascites accumulation by repeated intraperitoneal administrations of a Viscum album extract.

•  Bar-Sela G ,

•  Goldberg H ,

•  Beck D ,

•  Amit A ,

•  Kuten A .

Department of Oncology, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa , Israel . g_barsela@rambam.health.gov.il

BACKGROUND: Malignant ascites is a major problem in the management of advanced stages of certain malignancies. The possibility of reducing the accumulation of ascites by intraperitoneal injections of a Viscum album extract (Iscador M) was evaluated. PATIENTS AND METHODS: Twenty-three patients, with end-stage malignancies of varying histology, requiring repeated peritoneal punctures, were eligible for analysis. The time-interval between the first two punctures was measured and defined as the baseline. Following each subsequent puncture, Iscador M 10 mg was injected intraperitoneally. The intervals between later punctures were compared to previous intervals. RESULTS: Following the first injection, the median time-interval between injections increased from 7 to 12 days, reaching 13 days after the second injection. No toxicity was observed. CONCLUSION: This phase II study suggests that installation of Iscador M into the peritoneal cavity may reduce the need for repeated punctures. A randomized trial is needed to confirm these promising preliminary results.

PMID: 16739342 [PubMed - indexed for MEDLINE]

 

[v] Anticancer Res. 2006 Mar-Apr;26(2B):1519-29.

Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial.

•  Semiglazov VF ,

•  Stepula VV ,

•  Dudov A ,

•  Schnitker J ,

•  Mengs U .

Petrov Research Institute of Oncology, St. Petersburg , Russia .

The objective of this randomised, multicentre, double-blind clinical trial was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to mistletoe lectins, on quality of life (QoL) in breast cancer patients. A total of 352 patients were randomly allocated to 2 groups receiving PS76A2 (15 ng mistletoe lectin/0.5 ml) or matching placebo twice weekly for 4 to 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy followed by 2 months follow-up. The primary efficacy end-point was the change from baseline of 3 FACT-G subscales (physical, emotional and functional well-being) during the fourth CMF cycle. Secondary measures included GLQ-8 (8 linear analogue self-assessment scales), Spitzer's uniscale and haematological variables. The main variables of safety analysis were adverse events, including injection site reactions and clinical laboratory tests. The results showed that physical, emotional and functional well-being improved upon PS76A2, but deteriorated following placebo. The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G, which was analysed as O'Brien's rank sum of its 3 subscales: The total score increased by 4.40 +/- 11.28, indicating a higher QoL after PS76A2, but decreased by 5.11 +/- 11.77 with placebo (p<0.0001). The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 (sum of item nos. 1, 5, 6, 7, 8) and GLQ-3 (sum of item nos. 2, 3, 4). GLQ-5 characterises typical aspects of QoL, while GLQ-3 consists of 3 side-effects of CMF (feeling sick, numbness or pins and needles, loss of hair). GLQ-5 decreased by 42.9 +/- 125.0 upon PS76A2, indicating an improvement in QoL, but increased by 60.3 +/- 94.0 upon placebo (p<0.0001). GLQ-3 deteriorated in both groups (PS76A2: 13.9 +/- 52.4; placebo: 34.5 +/- 57.0), but the differences in favour of PS76A2 were, nevertheless, statistically significant (p=0.0007). The total score GLQ-8 improved by 28.9 +/- 154.6 after PS76A2 and deteriorated by 94.8 +/- 141.1 after placebo (p<0.0001). Spitzer's uniscale improved by 12.2 +/- 30.7 upon PS76A2 and deteriorated by 10.8 +/- 26.1 with placebo (p<0.0001). After follow-up without chemotherapy, a significant treatment difference in favour of PS76A2 was determined by means of FACT-G, GLQ-8 and Spitzer's uniscale. PS76A2 was well tolerated in this trial, with the exception of slight local reactions in 17.6% of the PS76A2 group. In conclusion, PS76A2 (15 ng mistletoe lectin/0.5 ml twice weekly) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up.

PMID: 16619567 [PubMed - indexed for MEDLINE]

 

[vi] Arzneimittelforschung. 2006 Jun;56(6A):457-60

Nitric oxide involvement in the anti-tumor effect of mistletoe (Viscum album L.) extracts Iscador on human macrophages.

•  Mossalayi MD ,

•  Alkharrat A ,

•  Malvy D .

Laboratoires d'Immunologie et Parasitologie, UFR Pharmacie, Universite Victor Segalen Bordeaux II, Bordeaux , France .

Lectins from different types of mistletoe (Viscum album, VA) have cytotoxic and immunomodulatory properties that may be relevant in the inhibition of tumor growth. The mechanism of this anti-tumoral activity remains unknown, although recent investigations point out the induction of anti-tumoral cytotoxic T cell activation. In this study therapeutically available mistletoe extracts (Iscador) prepared from Quercus (VA-Q), apple (Malus, VA-M) or pine (Pinus, VA-P) were used to investigate their capacity to induce tumor regression through the modulation of another T helper-1 (Th-1)-mediated anti-tumoral activity: the activation of macrophages. Macrophages are essential targets for both pro- or anti-inflammatory drugs and constitute an essential member of the anti-tumoral immune response. Freshly isolated human monocyte-derived macrophages are activated and various VA extracts are directly incorporated to cultures to assay their properties on the inflammatory and/or tumor cytotoxic responses. The data indicate that immunomodulatory activities of VA extracts differ according to their origin. VA-M and VA-P were able to increase anti-tumoral activity of activated human macrophages, with a possible role for nitric oxide in this effect.

PMID: 16927526 [PubMed - indexed for MEDLINE]

 

[vii] Arzneimittelforschung. 2006 Jun;56(6A):483-96.

Gene expression profiles of different breast cancer cells compared with their responsiveness to fermented mistletoe (Viscum album L.) extracts Iscador from oak (Quercus), pine (Pinus), white fir (Abies) and apple tree (Malus) in vitro.

 

* Eggenschwiler J,

* Patrignani A,

* Wagner U,

* Rehrauer H,

* Schlapbach R,

* Rist L,

* Ramos MH,

* Viviani A.

 

HSW, Hochschule Wadenswil, Wadenswil , Switzerland .

 

Cytotoxicity assays in vitro (MTT test) showed that the different breast cancer cell lines Kpl-1, MCF-7 and Mfm-223 respond differently to the mistletoe (Viscum album L.) preparations Iscador. Quercus (Qu), Abies (A), Malus (M) and Pinus (P). In order to determine the differences in the responsiveness of the cells more exactly, the gene expression profiles were determined by cells, which were treated with Mistletoe extracts, compared with untreated control cells. Such differences can be analysed in more detail by looking at the gene expression using Human Whole Genome microarray chips (41,000 genes). The results of the transcriptome analyses suggested that Iscador preparations influenced the overregulation of genes regarding immune defense, stress response, apoptosis and cell-cell adhesion pathways. Within the Mfm-223-Zellen was the Genexpression in MCF-7 and Kpl-1. The MCF-7 cells were affected on the genes which are involved in cell-cell contacts whereas Kpl-1 responded to the mistletoe extracts by changing the mRNA levels of the immune and stress response pathways. Concerning the effects of the mistletoe extract, we conclude that Iscador Qu and M have a greater influence on the immune defense and stress response genes whereas Iscador A tends to affect the cell-cell adhesion and cytoskeleton pathways. In summary, cDNA microarray analyses give us information on whether a cancer cell is sensitive to mistletoe extracts in relation to how many genes are significantly overrepresented after mistletoe treatment, and whether a particular mistletoe extract is more effective on a specific cancer cell than the other preparation.

 

PMID: 16927530 [PubMed - indexed for MEDLINE]

 

 

[viii] Arzneimittelforschung. 2006 Jun;56(6A):467-73.

Cytostatic and cytocidal effects of mistletoe (Viscum album L.) quercus extract Iscador.

 

* Kovacs E,

* Link S,

* Toffol-Schmidt U.

 

Verein fur Krebsforschung, Institute Hiscia, Arlesheim , Switzerland . evakovacsbenke@hotmail.com

 

Mistletoe (Viscum album) extract (Iscador) is used either alone or in combination with chemotherapy or radiotherapy in the treatment of tumor patients. In this study the effects of Viscum album Quercus (VA Qu) extract (1000 ng lectin and 6 microg viscotoxin/ml) in various doses were investigated in an in vitro model with tumor cells: three multiple myeloma (MM) cell lines (OPM-2, RPMI-8226, U-266) and three B cell lymphoma cell lines (U-698, DOHH-2, WSU-1). None of the three B lymphoma cell lines and none of the three multiple myeloma cell lines produced interleukin (IL)-6 spontaneously or after treatment with VA Qu extract. All three multiple myeloma cell lines expressed surface IL-6R and gp130, the B cell lymphomas expressed only gp130. Viscum album/Qu extract markedly downregulated the membrane expression of IL-6R and gp130 in RPMI-8226 (down to 29% and 32%) and the expression of gp130 in WSU-1 (down to 22%). There was a marked reduction of viable cells of RPMI-8226 (down to 28%) and WSU-1 (down to 8 %) at 100 microg/10(6) cells /ml. There was a clear relationship between the inhibition of proliferation and viability: the percentage reductions of the viable cells at 48 and 72 h were similar to those of proliferation at 24 and 48 h, respectively. This means that firstly the proliferation of the tumor cell is inhibited and then afterwards these cells die by apoptosis or necrosis. The inhibitory effect of VA Qu on the proliferation can be termed cytostatic, on the survival cytocidal. VA Qu was more effective in cells having a high proliferation rate than in those with a low proliferation rate. The effective dose range lay between 25 and 100 microg/10(6) cells/ml (5-20 ng lectin/10(6) cells/ml) for all parameters.

 

PMID: 16927528 [PubMed - indexed for MEDLINE]

 

 

[ix] Arzneimittelforschung. 2006 Jun;56(6A):474-82.

Effects of mistletoe (Viscum album L.) extracts Iscador on cell cycle and survival of tumor cells.

 

* Harmsma M,

* Ummelen M,

* Dignef W,

* Tusenius KJ,

* Ramaekers FC.

 

MUbio Products B.V, Maastricht , The Netherlands .

 

The molecular and cellular mechanisms by which mistletoe (Viscum album L.) extracts exert cytotoxic and immunomodulatory anti-tumoral effects are largely unknown. In this study the hypothesis that Iscador preparations induce tumor regression by cell cycle inhibition and/or interference with apoptotic signaling pathways in cancer cells was investigated. Also a possible effect on angiogenesis, which is a prerequisite for tumor growth in vivo, is studied in endothelial cell cultures. Furthermore, it was examined which apoptotic signaling route(s) is (are) activated by Iscador by studying specific pro-apoptotic proteins in cultured cells. To characterize these properties, 9 human cancer cell lines of different origin, one epidermis derived cell line and 2 endothelial cell cultures were incubated with different concentrations of Iscador Quercus Spezial and Iscador Malus Spezial. Cell cycle kinetic parameters were measured by bromodeoxyuridine (BrdU) pulse labeling and tubulin staining. Apoptotic responses were detected by M30 Cyto-Death or Annexin V/propidium iodide assays. Characterization of the apoptotic pathway(s) was performed by staining cells for amongst others active caspase 3 and cytochrome C (mitochondrial pathway), as well as active caspase 8 (death receptor pathway). The sensitivity to Iscador treatment varies strongly between different cell lines and also ing those derived from small cell lung cancer, and adenocarcinoma of the lung and breast, as well as endothelial cell cultures, Iscador caused early cell cycle inhibition followed by apoptosis in a dose dependent manner. Amongst the low responders are cell lines derived from colorectal carcinoma. In general Iscador Malus exerted a stronger response than Iscador Quercus. Apoptosis was induced by activating the mitochondrial but not the death receptor dependent pathway, at least in case of Iscador Quercus. Iscador Malus also seemed to induce apoptosis via the death receptor route, which may explain the higher sensitivity of cancer and endothelial cells to this preparation.

 

 

[x] J Clin Immunol. 2006 Jul;26(4):347-59. Epub 2006 May 17.  

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

•  Heinzerling L ,

•  von Baehr V ,

•  Liebenthal C ,

•  von Baehr R ,

•  Volk HD .

Department of Medical Immunology, Charite - University Hospital , Berlin , Germany . lucie.heinzerling@charite.de

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.

PMID: 16705487 [PubMed - indexed for MEDLINE]

 

 

[xi] Anticancer Res. 2006 Sep-Oct;26(5A):3485-92.

Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe) preparations.

•  Zuzak TJ ,

•  Rist L ,

•  Eggenschwiler J ,

•  Grotzer MA ,

•  Viviani A .

University of Applied Sciences, Waedenswil , Switzerland . tycho.zuzak@kispi.unizh.ch

BACKGROUND: Medulloblastoma constitute more than 20% of all paediatric brain tumours and are the most common malignant brain tumours in children. Adjuvant chemotherapy has seen a strong increase in the use of complementary medicine for cancer treatment. Evidence for cytotoxic and apoptotic effects of Viscum album (Mistletoe) in vitro is available, however, no data concerning paediatric tumours, especially paediatric brain tumours, has been provided so far. MATERIALS AND METHODS: In order to compare the receptiveness of medulloblastoma cells to different Viscum album preparations, in vitro cytotoxic effects of eight Viscum album extracts on four different paediatric medulloblastoma cell lines were analysed by MTT-Tests. Lectin contents of the extracts were determined to correlate them with the mitochondrial activity of mistletoe-treated cells. Flowcytometric analyses with Annexin V-FITC staining were carried out to quantify the amount of apoptotic cells compared to necrotic and viable cells. RESULTS: Data obtained with the medulloblastoma cell lines, Daoy, D342, D425 and UW-288-2, treated with Viscum album preparations from eight dissimilar host trees (Iscucin Abietis, Pini, Populi, Mali, Salicis, Crataegi, Quercus and Tiliae), indicated a significant growth-inhibition of all cell lines, yet the cell susceptibility was dissimilar against the different extracts. The decrease in mitochondrial activity and increase in apoptosis correlated with the lectin content of the used preparation in a dose-dependent manner. CONCLUSION: These in vitro results show that paediatric medulloblastoma cells respond to Viscum album preparations, by undergoing cell death through apoptosis and that this growth-inhibition correlates with the lectin content of the used preparation.

PMID: 17094471 [PubMed - in process

 


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