Sei sulla pagina 1di 17

The Longwood Herbal Task Force

(http://www.mcp.edu/herbal/default.htm) and
The Center for Holistic Pediatric Education and Research
(http://www.childrenshospital.org/holistic/)

Mistletoe (Viscum album L.)


Margaret E. Loeper, MS

Principal Proposed Uses: Antineoplastic, immunostimulant


Other Proposed Use: Antihypertensive

Overview
The major use of mistletoe, Viscum album, is as a palliative cancer therapy. Historically it
has been used to treat hypertension, epilepsy, exhaustion, anxiety, arthritis, vertigo, and
degenerative inflammation of the joints. V. album is the European mistletoe species; it is the
species used in the treatment of cancer and it will be the focus of this monograph. Phoradendron,
or American mistletoe, is rarely used medicinally. Both species contain lectins, protein toxins,
and polysaccharides. The scientific evidence regarding mistletoe’s use as a palliative cancer
therapy is inconclusive but promising. Mistletoe extracts are usually given parenterally and may
cause inflammation at the injection site. Side effects from ingestion of mistletoe include
gastrointestinal symptoms such as nausea, vomiting and diarrhea. Poisonings of children after
mistletoe ingestion have been reported. There are no data on mistletoe’s safety during pregnanc y
or lactation.

Historical and Popular Uses


Washington Irving described the tradition of stealing a kiss under this intriguing plant:
“...the mistletoe, with its white berries,” he said, is “hung up, to the imminent peril of all the
pretty housemaids.” At Christmas, the young men had the privilege of kissing ladies under
mistletoe, “plucking each time a berry from the bush.” Once all the berries had been plucked, no

more kissing was allowed1.


First described by the Greek naturalist Theophrastus in the Third Century BC, mistletoe

Margaret E. Loeper, MS Mistletoe Page 1


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
became embedded in European rituals, folklore, and folk medicine. It was a sacred plant of the
Celtic peoples who dominated Europe in the first millennium BC. The Gauls and the Celts called
it “all- healer” or “cur e-all”2.
Both European and American mistletoe contain toxic proteins which are similar in their
chemical composition and produce similar effects, including hypotension, bradycardia, and

vasoconstriction, in test animals 3. Despite the popular belief that the two types of mistletoe have

opposite effects, the stems and leaves of these plants contain similar phytochemicals4.
Anthroposophist Rudolf Steiner introduced the use of mistletoe extracts for the treatment

of cancer in 19165. Nowadays, Europeans include V. album in oncology therapies under the
trade names Iscador and Helixor. The German Commission E has approved mistletoe as a
treatment for degenerative and inflamed joints and as a palliative therapy for malignant tumors.

Botany
Medicinal species: Viscum album
Common names: All heal, bird lime, birdlime mistletoe, devil’s fuge, European mistletoe, golden
bough, herb de la croix (Fr), lignum crucis, mystyldene, visci albi fructus (berrie s), visci

albi herba (leaves), visci albi stipites (stem), and viscum6-10

Botanical family: Loranthaceae11


Plant description: Mistletoe is a semi-parasitic woody perennial commonly found growing on

oaks and other deciduous trees7, 10. The plant is small, dioecious and shrubby, with
oblong evergreen leathery entire leaves, clear dichasial branching and four-part flowers

which form white sticky berries. It has a faint but characteristic odor and a bitter taste8.
Viscum is most commonly seen on old apple, ash, and hawthorn trees; although mistletoe
does not grow as well on oak trees, mistletoe from oak trees has traditionally been the

most commonly used12. Mistletoe is propagated by birds that eat the berries and then
excrete the seeds, or smear them on branches by wiping the sticky pulp off their beaks.
Under proper conditions, the seeds germinate and the roots penetrate the branch of the
host tree. Mistletoe is considered a semiparasitic plant because it synthesizes its own
chlorophyll but depends on the host for its supply of water and minerals. The parts used
medicinally are the leaves and stems.

Margaret E. Loeper, MS Mistletoe Page 2


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
Where it’s grown: V. album is native to Europe and Asia. Imports originate in Bulgaria, Turkey,

the former Yugoslavia, Albania and the former USSR8. V. album grows in Europe,
northwest Africa, and southwest and central Asia and Japan; the Asian plant is a special
variety, V. album (L) var. coloratum. V. album is grown in the US in Sonoma County,
California; it is not imported13. American mistletoe grows in the eastern US from New
Jersey to Florida, and from southern Ohio to southern Indiana. It is prevalent in Texas
and some species are common in California and Oregon.

Biochemistry
Mistletoe (Viscum album): Active Chemical Constituents
• Glycoproteins: mistletoe lectins I (galactoside-specific lectin), II, and III
• Proteins: viscotoxin
• Polysacchrides: galacturonan, arabinogalactan
• Alkaloids

Mistletoe’s lectins are cytotoxic glycoproteins of approximately 10,000 molecular

weight; they cause cells to agglutinate14 and inhibit protein synthesis on the ribosomal level.
The lectins, also known as viscumin or agglutinin, are dual chain molecules. Chain A inhibits
protein synthesis and chain B activates macrophages and releases lymphokines from
lymphocytes. Both the A and B chains of mistletoe lectin I also inhibit allergen- induced

histamine release from leukocytes and collagen-induced serotonin release from platelets14.
Lectins are structurally similar to two highly biologically active toxic proteins, ricin and abrin.
The amounts and biological activity of V. album lectins are dependent on the host tree,

manufacturing process, and time of harvest15.


Viscotoxin is a 46-amino acid peptide that damages cell membranes. Viscotoxin is found
only in V. album. A similar constituent of Phoradendron is phoratoxin, a polypeptide about
twice the weight of viscotoxin; it makes up 0.01% to 0.23% of Phoradendron leaves and
stems 16.
Various polysaccharides are thought to be involved in mistletoe’s antineoplastic effects.

Margaret E. Loeper, MS Mistletoe Page 3


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
The leaves and stems contain esterified galacturonan, while the berries contain primarily

arabinogalactan17.
Alkaloids are nitrogenous compounds that may contribute to mistletoe’s cytotoxicity14.

Margaret E. Loeper, MS Mistletoe Page 4


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
Experimental Studies
Mistletoe: Potential Clinical Benefits
1. Cardiovascular: Hypertension
2. Pulmonary: none
3. Renal and electrolyte balance: none
4. Gastrointestinal/hepatic: none
5. Neuro-psychiatric: Epilepsy, exhaustion, vertigo, and anxiety: Traditional uses, no data.
6. Endocrine: none
7. Hematologic: Coagulant : Traditional use, no data.
8. Rheumatologic: Degenerative inflammation of the joints: Traditional uses; no data.
9. Reproductive: Abortifacient : Traditional use of Phoradendron, no data
10. Immune modulation: Immunostimulant
11. Antimicrobial: none
12. Antineoplastic: Antineoplastic
13. Antioxidant: none
14. Skin and mucus membranes: none
15. Other/miscellaneous: none

1. Cardiovascular: Hypertension
i. In vitro data: none

ii. Animal data: Animal experiments are contradictory8.


iii. Human data: A small case series in hypertensive adults treated with an herbal
combination including V. album reported decreased blood pressure over 3-5 months.
Since an herbal combination was used, it is difficult to interpret the effects of V. album
alone 18. There are no controlled trials evaluating V. album as a sole antihypertensive or
comparing it to standard medications.
2. Pulmonary: none
3. Renal and electrolyte balance: none
4. Gastrointestinal/hepatic: none
5. Neuro-psychiatric: Epilepsy, exhaustion, vertigo, and anxiety: Traditional uses, no data10.

Margaret E. Loeper, MS Mistletoe Page 5


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
6. Endocrine: none

7. Hematologic: Coagulant : Traditional use, no data10.


8. Rheumatologic: Degenerative inflammation of the joints: Traditional use, no data8.
9. Reproductive: Abortifacient : Phoradendron has been recommended by herbalists as an
abortifacient. No data are available.
10. Immune modulation: Immunostimulant
i. In vitro data: V. album agglutinin, a galactoside-specific plant lectin, induced apoptosis
in human and murine lymphocytes and monocytes19 and stimulated the proliferation of

hematopoietic progenitor cells from healthy volunteers20. Mistletoe extracts induced


proliferation of peripheral blood mononuclear cells; the strongest proliferation was seen

with mistletoe from apple trees21. CD4+ T cells exposed to mistletoe extract displayed a

significant increase in mean velocity, time locomoting, and migration distance22, 23.
ii. Animal data: none
iii. Human data: Case series and controlled trials in healthy adults and cancer patients
support the use of mistletoe as an immunostimulant. In six healthy volunteers given
mistletoe extract for eight weeks, there was pronounced proliferation of peripheral

mononuclear cells24. See also Antineoplastic.


11. Antimicrobial: none
12. Antineoplastic: Antineoplastic
i. In vitro data: Mistletoe lectins cause both apoptosis and direct cytotoxicity25. Mistletoe
lectins triggered apoptosis and enhanced the cytotoxic effect of chemotherapeutic drugs

in leukemic cell lines26. V. album extracts had significant cytotoxic activity against
cultured Hep-2 cells27. Mistletoe (Iscador) inhibited the growth of rat hepatoma cells

and Molt 4 cells in tissue culture28. Mistletoe lectins inhibited the growth of the Molt 4

tumor cell line; mistletoe lectin III was the most potent inhibitor29. Normal Molt 4 cells
30
and three drug-resistant sublines were sensitive to the cytotoxic effects of Helixor .
Mistletoe lectins I, II, and III exerted cytotoxic effects against six human breast cancer
cell lines31. All mistletoe lectins inhibited leukemia cell growth; mistletoe lectin III was

approximately ten times as cytotoxic as lectin I32.

Margaret E. Loeper, MS Mistletoe Page 6


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
Mistletoe extract significantly reduced the DNA damaging effects of

carcinogens 33.
In a study comparing 12 different mistletoe preparations on human leukocytes, the
different preparations had varying effectiveness in inducing apoptosis and cytokine
production. However, there was no correlation between the biological effects and the

lectin content of these different preparations 34.


ii. Animal data: The Viscum album preparation Isorel significantly restored the suppressed

immune response of fibrosarcoma-bearing mice35.


Mistletoe preparations were effective in fighting solid tumors in eight of ten
animal studies (seven in mice and three in rats). In two studies in mice, an ext ract of V.
album coloratum (Korean mistletoe) significantly inhibited metastases including lung
metastases36, 37. Iscador M, an extract of Viscum album, inhibited metastatic colony

formation induced by melanoma cells and reduced mortality in mice38. When Iscador
was administered to mice simultaneously with melanoma cells, lung nodule formation
was inhibited by 92% and there was a 71% increase in life span38. Mistletoe lectin I

significantly reduced tumor volume in rats with glioma 39. It reduced tumor volume and

lung and liver metastases in mice40. A single injection of the V. album preparation
Isorel reduced tumor size and caused tumor necrosis41. Another mistletoe preparation

had antimetastatic activity against B16 melanoma lung colonization42.


In two negative studies in rats, mistletoe lectin I did not inhibit chemically-

induced bladder cancer43, 44, and did not stimulate significant cellular immunological
reaction in the wall of normal or cancerous urinary bladder43.
iii. Human data: In case series and controlled trials, mistletoe had immunostimulant effects

in cancer patients. Studies of its effects aga inst cancer have had conflicting results.45-49
In several small case series, cancer patients given parenteral V. album
preparations (in doses ranging from 0.5 ng/kg to 1 mg/kg) had increases in natural killer
cells, T-helper cells, cytokine release, and peripheral blood mononuclear cells and
lymphocytes. In one of these series, V. album treatment was associated with an improved

quality of life48.

Margaret E. Loeper, MS Mistletoe Page 7


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
In a prospective randomized clinical trial of 35 patients with stage II-IV glioma,
the treatment group received standard treatment plus a mistletoe extract (1 ng mistletoe
lectin I/kg twice weekly) for three months beginning the day after surgery. The control
group received standard therapy. The group receiving mistletoe had a significant up-
regulation of cell counts (CD 3, CD-4, and CD-8 cells) and activities (CD-25, HLA/DR-
positive cells) after three months compared to preoperative values, whereas the control

group remained at preoperative values50.


In a prospective randomized clinical study of 47 breast cancer patients, those
given mistletoe lectin I (0.5-1.0 ng/kg twice weekly) had enhanced activity of peripheral
blood natural killer cells and T–lymphocytes15.
Studies of mistletoe’s antineoplastic effects have had conflicting results.
A 59-year-old man with small cell lung carcinoma opted for Iscador treatment
rather than chemotherapy. He received subcutaneous Iscador once daily for five days,
followed by oral Iscador 0.05–0.1 mg three times a day. The dose was progressively
increased over a few weeks to achieve a maintenance dose of 5-10 mg three times a day.

Subsequently radiotherapy was given and the patient lived five and a half years51
In 16 patients with stage III or IV ductal pancreatic carcinoma, Eurixor (1 ng/kg)
was administered twice weekly by subcutaneous injection. No partial or complete
remissions were seen, but all but two patients claimed that mistletoe had a positive effect

on their quality of life, with a decline only in the last few weeks of life52.
Fourteen patients with untreated stage IV renal adenocarcinoma and lung
metastases were treated with escalating subcutaneous doses of Iscador over three weeks.

All the patients died, and no response to treatment was noted53.


In a retrospective analysis of 991 patients with colorectal cancer, mistletoe
treatment significantly decreased the recurrence rate by 13% in those with lymph node
negative disease, and by 23% in those with lymph node positive disease, in comparison to
the untreated group. The survival probability as a result of the mistletoe therapy was 340

days longer than in the untreated group 54.


13. Antioxidant: none
14. Skin and mucus membranes: none

Margaret E. Loeper, MS Mistletoe Page 8


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
15. Other/miscellaneous: none

Margaret E. Loeper, MS Mistletoe Page 9


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
Toxicity and Contraindications
All herbal products carry the potential for contamination with other herbal products, pesticides,
herbicides, heavy metals, and pharmaceuticals. This is particularly concerning with imports
from developing countries.
Furthermore, allergic reactions can occur to any natural product in sensitive persons

Allergic reactions to mistletoe have been reported. A case of allergic rhinitis has been reported in

a subject handling commercial mistletoe tea7


Potentially toxic compounds in mistletoe: Lectins, viscotoxin. All parts of the plant contain toxic
compounds.
Acute toxicity: The German Commission E reports side effects such as chills, fever, headaches,
angina and hypotension9. Ingestion of the American Phoradendron species usually
causes acute gastrointestinal symptoms; lectins in both Viscum and Phoradendron species
may cause delayed gastroenteritis. Ingesting concentrated mistletoe extracts may produce
serious poisonings. Symptoms of acute toxicity include nausea, diarrhea, fixed and
dilated pupils, diplopia, irritated conjunctiva, bradycardia, vasoconstriction, hypo- or
hypertension, seizures, delirium and hallucinations. Cardiac arrest may occur. Deaths

have occurred after ingestion of mistletoe tea taken as a tonic or abortifacient 55-59.
In 300 cases of ingestion of mistletoe leaves or berries, the majority of patients
remained asymptomatic and no deaths occurred; ingestion of up to three berries or two

leaves is unlikely to produce serious toxicity7. Of the 1754 exposures to Phoradendron


leucarpum reported between 1955-1992, no fatalities occurred, and 90.3% of those

exposed remained asymptomatic. Children accounted for 92.1% of the cases60.


Intradermal injection of mistletoe may cause local inflammation, which can

develop into necrosis8.

Chronic toxicity: Lectins are cytotoxic by inhibiting protein synthesis at the ribosomal level 14,
61, 62. One case of hepatitis has been reported after ingestion of an herbal compound

containing mistletoe, but no other instances of hepatotoxicity have been documented for
mistletoe, and hepatitis has been documented with a common contaminant of scullcap,

which was also in the herbal compound 11.

Margaret E. Loeper, MS Mistletoe Page 10


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
Limitations during other illnesses or in patients with specific organ dysfunction: Herbalists
recommend avoiding mistletoe in patients with chronic progressive infections such as
tuberculosis. Persons with heart disease should be monitored when using mistletoe,
because it may cause hypertension or hypotension.
Interactions with other herbs or pharmaceuticals: Mistletoe may interfere with existing cardiac

or immunosuppressant therapies11. Mistletoe is contraindicated in patients taking

monamine oxidase (MAO) inhibitors because mistletoe preparations contain tyramine14.


Safety during pregnancy and/or childhood: Mistletoe has not been approved for pediatric use or
use during pregnancy or lactation. It is contraindicated during pregnancy due to its
speculated uterine stimulant action63.

Margaret E. Loeper, MS Mistletoe Page 11


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
Typical Dosages
Provision of dosage information dose NOT constitute a recommendation or endorsement, but
rather indicates the range of doses commonly used.
Doses are given for single agent use and must be adjusted when using remedies in combinations.
Doses may also vary according to the type and severity of the condition treated and individual
patient conditions.

Typical adult doses: Dosing parameters have not been established. Dosage depends on a number
of factors including as the host tree, the preparation method, and standardization of the
product to a particular constituent. Overdoses may cause poisoning.
Tea (cold water infusion): Cold water poured over 2.5 g (1 tsp.) of finely chopped drug
and allowed to stand at room temperature for 10 to 12 hours, then strained. One to

two cups daily. Mistletoe is also available in tea bags9


Tincture (1:5 in 45% alcohol): 1-4 ml daily12, 64.

Dried aqueous extract (4:1): 100-250 mg daily12

Fluid extract (1:1 in 25% alcohol): 1-3 ml three times daily11


“Blood pressure tea”: Mistletoe leaves, hawthorn leaves and flowers, and melissa leaves
in equal parts. Two cups daily prepared by infusing 2 teaspoons of the mixture for
five to ten minutes65.
Oral Iscador: The following regime was used in one case study: 0.05-0.1 mg three

times daily, then titrated over two weeks to 5-10 mg three times daily51.
Parenteral preparations with standardized concentrations of mistletoe lectin I: 0.29-12

ng/kg per day48, 66. In some studies the optimal dose was considered to be 1
nanogram per kilogram given twice weekly48, 52, 67.
Parenteral fresh plant extract: Based on whole fresh plant, dosages have ranged from 1
to 200 mg subcutaneously daily for up to two years. IV doses ranging from 0.09
to 0.33 mg per kg per day of fresh plant equivalent have been given as single or

daily doses in 250 ml of saline49.


Pediatric dosages: Unknown
Brand names: European brands include: Iscador and Helixor, for subcutaneous use in cancer
Margaret E. Loeper, MS Mistletoe Page 12
Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
treatment, and Plenosol, for parenteral use for arthritic joints65, 68.
Availability: Injectable forms are available only in Europe. Powdered herb capsules are available

in the US 3. While Iscador is not commonly used in the US, and is not approved for sale
in the United States, but US doctors can order it directly from European manufacturers.
American patients may also travel to Europe for Iscador treatment. Mistletoe therapy is
available at clinics, hospitals, and private practices in the United Kingdom, Switzerland,

West Germany, and the Netherlands2.


Dosages used in combinations: Mistletoe is a component of antihypertensive medications,
cardiotonics and sedatives. Except for the mistletoe tea combination noted above, the

mistletoe dosages used in these combinations are unknown8.

Margaret E. Loeper, MS Mistletoe Page 13


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
REFERENCES

1. Bowman IA. The everlasting mistletoe and the cardiovascular system. Herbal Gram 1992; 26:16-21.
2. Walters R. Herbs and plants against cancer. Journal of the A merican Holistic Verterinary Medical
Association 1994; 13:30-38.
3. Tyler VE. The honest herbal : a sensible guide to the use of herbs and related remedies. New York:
Pharmaceutical Products Press, 1992:xviii, 375.
4. Anonymous. Monographs on the medicinal uses of plants. Exeter: European Scientific Cooperative on
Phytotherapy, 1997.
5. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. Berlin:
Springer, 1997:306.
6. Peirce A. The American Pharmaceutical Association practical guide to natural medicines. New York:
William Morrow and Company, Inc., 1999.
7. Anonymous. The Lawrence Review of Natural Products. In: Charles Dombek R, MA, ed. Facts and
Comparisons. St. Louis: J.B. Lippencott Company, 1992.
8. Bissett NG. He rbal drugs and phytopharmaceuticals. Stuttgart: MedPharm CRC Press, 1994:566.
9. Blumenthal M. The complete German Commission E monographs : therapeutic guide to herbal medicines.
Austin: American Botanical Council, 1998.
10. Fleming T. PDR for herbal medicines. Montvale, NJ: Medical Economics Company, Inc., 1998.
11. Newall CA, Anderson LA, Phillipson JD. Herbal medicines : a guide for health-care professionals. London:
Pharmaceutical Press, 1996:ix, 296.
12. Murray MT. The healing power of herbs : the enlightened person's guide to the wonders of medicinal
plants. Rocklin, CA: Prima Pub., 1995:xiv, 410.
13. Becker H. Botany of European Mistletoe (viscum album L). Oncology 1986; 43:2-7.
14. Franz H. Mistletoe Lectins and Their A and B Chains. Oncology 1986; 43:23-34.
15. Bussing A, Schietzel M. Apoptosis -inducing properties of Viscum album L. extracts from different host
trees, correlate with their content of toxic mistletoe lectins. Anticancer research 1999; 19:23-28.
16. Andersson K, Johannsson M. Effects of viscotoxin on rabbit heart and aorta,and on frog skeletal muscle.
European Journal of Pharmocology 1973; 23:223-231.
17. Jordan E, Wagner H. Structure and properties of polysaccharides from Viscum album (L). Oncology 1986;
43:8-15.
18. Fletcher-Hyde F. Herbal Remedies Influencing the Heart and Circulation. Part 2 (Hypertension). The
British Journal of Phytotherapy 1990; 1:14-16.
19. Hostanska K, Hajto T, Weber K, et al. A natural immunity-activating plant lectin, Viscum album
agglutinin-I, induces apoptosis in human lymphocytes, monocytes, monocytic THP-1 cells and murine
thymocytes. Natural Immunity 1996; 15:295-311.
20. Vehmeyer K, Hajto T, Hostanska K, et al. Lectin-induced increase in cologenic growth of haematopoietic

Margaret E. Loeper, MS Mistletoe Page 14


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
progenitor cells. European Journal Haematology 1998; 60:16-20.
21. Fischer S, Scheffler A, Kabelitz D. Stimulation of the specific immune system by mistletoe extracts. Anti-
Cancer Drugs 1997; 8:S33-S37.
22. Nikolai G, Friedl P, Werner M, Niggeman B, Zanker K. Effect of a mistletoe extract (Iscador QuFrF) on
viability and migratory behavior of human peripheral CD4+ and CD8+ T lymphocytes in three-dimensional
collagen lattices. In Vitro Cell Dev Biol Anim 1997; 33:710-716.
23. Schiltze J, Stettin A, Berg P. Demonstration of specifically sensitized lymphocytes in patients treated with
an aqueous mistletoe extract (Viscum album L.). Klin Wochenschr 1991; 69:397-403.
24. Stein G, Berg P. Modulation of cellular and humoral immune responses during exposure of healthy
individuals to an aqueous mistletoe extract. Eur Journal Med Res 1998; 3:307-314.
25. Bussing A, Suzart K, Bergman J, Pfuller U, Schietzel M, Schweizer K. Induction of apoptosis in human
lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. Cancer Letters 1996;
1999:59-72.
26. Bantel H, Engels I, Voelter W, Schilze -Osthoff K, Wesselborg S. Mistletoe lectin activates caspase-
8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis.
Cancer Research 1999; 59:2083-90.
27. Saenz M, Ahumada M, Garcia M. Extracts from Viscum and Crataegus are cytotoxic against larynx cancer
cells. Z Naturforsch [C] 1997; 52:42-44.
28. Ribereau-Gayon G, Jung M-L, DiScala D, Beck J-P. Comparison of the Effects of Fermented and
Unfermeted Mistletoe Preparations on Cultured Tumor Cells. Oncology 1986; 43:35-41.
29. Dietrich J, Ribereau-Gayon G, Jung M, Franz H, Bech J, Anton R. Identity of the N-terminal sequences of
the three A chains of mistletoe (Viscum album L.) lectins: homology with ricin-like plant toxins and single-
chain ribosome-inhibiting proteins. Anticancer Drugs 1992; 3:507-11.
30. Hulsen H, Mechelke F. In Vitro Effectiveness of a Mistletoe Preparation on Cytostatic-Drug-Resistant
Human Leukemia Cells. Naturwissenschaften 1987; 74:1987.
31. Schumacher U, Stamouli A, Adam E, Peddie M, Pfuller U. Biochemical, histochemical and cell biological
investigations on the actions of mistletoe lectins I, II, and III with human breast cancer cell lines. Glycoconj
1995; 12:250-257.
32. Ribereau-Gayon G, Jung M, Frantz M, Anton R. Modulation of cytotoxicity and enhancement of cytokine
release induced by Viscum album L. extracts or mistletoe lectins. Anticancer Drugs 1997; 8:s3-s8.
33. Bussing A, Jungmann H, Suzart K, Schweizer K. Supression of sister chromatid exchange-inducing DNA
lesions in clutered peripheral blood mononuclear cells by Viscum album L. Journal of Experimental &
Clinical Cancer Research 1996; 15:107-114.
34. Elsasser-Beile U, Lusebrink S, Grussenmeyer T, Wetterauer U, Schultze-Seemann W. Comparison of the
effects of various clinically applied mistletoe preparations on peripheral blood leukocytes.
Arzneimittelforschung 1998; 48:1185-1189.
35. Jurin M, Zarovic N, Borovic S, Kissel D. Viscum album L. preparation Isorel modifies the immune reponse

Margaret E. Loeper, MS Mistletoe Page 15


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
in normal and in tumour-bearing mice. Anticancer Drugs 1997; 8:S27-S31.
36. Yoon T, Yoo Y, Kang T, et al. Prophylactic effect of Koream mistletoe (Visum album coloratum) extract
on tumor metastasis is mediated by enhancement of NK cell activity. Int J Immunopharmacol 1998;
20:163-172.
37. Yoon T, Yoo Y, Choi O, et al. Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on
tumor angiogenesis and metastasis of haematogenous and non-haematogenous tumor cells in mice. Cancer
Letters 1995; 97:83-91.
38. Antony S, Kuttan R, Kuttan G. Effect of viscum album in the inhibition of lung metastasis in mice induced
by B16F10 melanoma cells. J Exp Clin Cancer Res 1997; 16:159-162.
39. Lenartz D, Andermahr J, Plum G, Menzel J, Beuth J. Efficiency of treatment with galactoside-specific
lectin from mistletoe against rat glioma. Anticancer Research 1998; 18:1011-1014.
40. Beuth J, Ko H, Gabius H, Pulverer G. Influence of treatment with the immunomodulatory effective dose of
the beta-galactoside-specific lectin from mistletoe on tumor colonization in BALB/c-mice for two
experimental model systems. In Vivo 1991; 5:29-32.
41. Zarkovic N, Zarkovic K, Grainca S, Kissel D, Jurin M. The Viscum album preparation Isorel inhibits the
growth of melanoma B16F10 by influencing the tumor-host relationship. Anticancer Drugs 1997; 8:S17-
S22.
42. Weber K, Mengs U, Schwarz T, et al. Effects of a standardized mistletoe preparation on metastatic B16
melanoma colonization in murine lungs. Arzneimittelforschung 1998; 48:497-502.
43. Kunze E, Schulz H, Gabius H. 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. J Cancer Res Clin Oncol 1998; 124:73-87.
44. Kunze E, Schulz H, Ahrens H, Gabius H. Lack of an antitumoral effect of immunomodulatory galactoside-
specific mistletoe lectin on N-methyl-N-nitrosourea-induced urinary bladder carcinogenesis in rats. Exp
Toxicol Pathol 1997; 49:167-180.
45. Beuth J, Stoffel B, Ko H, Tunggal L, Pulverer G. Immunoactive effects of various mistletoe lectin-1
dosages in mammary carcinoma patients. Arzneimittelforschung 1995; 45:505-507.
46. Beuth J, Ko H, Gabius H, Burrichter H, Oette K, Pulverer G. Behavior of lymphocyte subsets and
expression of activation markers in response to immunotherapy with galactoside-specific lectin from
mistletoe in breast cancer patients. Clinical Investigations 1992; 70:658-661.
47. Hajto. Immunomodulatory effects of Iscador: A Viscum album preparation. Oncology 1986; 43:51-65.
48. Heiny B, Beuth J. Mistletoe extract standardized for the Galactoside-Specific lectin (ML-1) induces beta-
endorphin release and immunopotentiation in breast cancer patients. Anticancer Research 1994; 14:1339-
1342.
49. Kovacs E, Hajto T, Hostanska K. Improvement of DNA Repair in Lymphocytes of Breast Cnacer Patients
Treated with Viscum album Extract (Iscador). European Journal of Cancer 1991; 27:1672-1676.
50. Lenartz D, Stoffel B, Menzel J, Beuth J. Immunoprotective Activity of the Galatoside-Specific Lectin from

Margaret E. Loeper, MS Mistletoe Page 16


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999
Mistletoe after Tumor Destructive Therapy in Glioma Patients. Anticancer Research 1996; 16:3799-3802.
51. Bradley G, Clover A. Apparent response of small cell lung cancer to an extract of mistletoe and
homoeopathic treatment. Thorax 1989; 44:1047-1048.
52. Friess H, Beger H, Kunz J, Funk N, Schilling M, Buchler M. Treatment of Advanced Pancreatic Cancer
with Mistletoe: Results of a Pilot Trial. Anticancer Research 1996; 16:915-920.
53. Kjaer M. Mistletoe (Iscador) Therapy in Stage IV Renal Adenocarcinoma. Acta Oncologica 1989; 28:489-
494.
54. Hellan J, Danmayer E, Hellan M. Importance of complementary medicine during the treatment of
oncological patients- SHown by the exa mple of colorectal carcinoma. Deutsche Zeitschrift fur Onkologie
1995; 27:85-94.
55. Dixon. British Medical Journal 1874; 1:255.
56. Osol A, Farrar G. US Dispensatory. Philadelphia: JB Lippencott Company, 1955:1928-1929.
57. Rhoads P, Banner W, Tong T, al e. Unanticipated neurologic symptoms following bee pollen. Bulletin
from the Arizona Poison Information Center. Tucson, Arizona, 1986.
58. Moore. Mistletoe poisoning: a review of the available literature and the report of a case of probable fatal
poisoning. Journal of South Carolina Medical Association 1969; 59:269-271.
59. Petkov. Plants with hypotensive, antiatheromatous, and coronary-dilating actions. American Journal of
Chinese Medicine 1979; 7:197-236.
60. Krenzelok EPJ, TD; Aronis, John. American Mis tletoe Exposures. American Journal of Emergency
Medicine 1997; 15:516-520.
61. Anon. Baleful Mistletoe. Lancet 1982; 1:295.
62. Salzer. Pleura carcinosis. Cytomorphogical findings with the mistle preparation Iscador and other
pharmaceuticals. Oncology 1986; 43:66-70.
63. Brinker FJ. Herb contraindications and drug interactions : with appendices addressing specific conditions
and medicines. Sandy, Or.: Eclectic Institute, 1997:146.
64. Hoffman D. The complete illustrated holistic herbal. Rockport, MA: Element Books Inc., 1996.
65. Weiss RF. Herbal medicine. Gothenburg, Sweden: AB Arcanum, 1988.
66. Hajto T, Hostanska K, Gabius H. Modulatory potency of the beta-galactoside-specific lectin from mistletoe
extract (Iscador) on the host defense system in vivo in rabbits and patients. Cancer Research 1989;
49:4803-4808.
67. Hauser. Unproven methods in oncology. European Journal of Cancer 1991; 27:1549-1551.
68. Wagner H, Jordan FB. Studies on the standardization of mistletoe preparations. Oncology 1986; 43:16-22.

Margaret E. Loeper, MS Mistletoe Page 17


Longwood Herbal Task Force: http://www.mcp.edu/herbal/default.htm Revised February 10, 1999

Potrebbero piacerti anche