The Viscum album is a semi parasitic plant that has been used for centuries to treat numerous human diseases. It is often used in Germany, where a variety of different extracts are produced in the form of injectables.

The Viscum album is one of the most widely studied complementary therapies for cancer. In some European countries, preparations made from Viscum album are among the most prescribed drugs for patients with this type of pathology.

viscum mistletoe cancro oncoogia integrativa iscador helixor

The album Viscum has a potential anticancer effect, extracts derived from Viscum have been shown to kill cancer cells in vitro [ 1-10 ] by negatively regulating the central genes involved in tumor progression, malignancy, migration and cell invasion such as TGF-β and matrix metalloproteinases [ 11 , 12 ].

Viscum extracts have enhanced lysis (death) of tumor cells mediated by Natural killer (NK) cells, reduce the migratory and invasive potential of tumor cells and stimulate immune system cells both in vitro and in vivo [ 10 – 31].

Three components of Viscum: viscotoxins, polysaccharides and lectins, may be responsible for these effects [ 10 , 13 – 15 , 19 , 21 , 23 – 25 , 32 – 39 ].

Viscotoxins are small proteins that exhibit cell-killing activity and possible immune system stimulating activity [ 1 , 6 , 20 , 21 , 40 , 41 ].

Lectins are complex molecules made of proteins and carbohydrates that are able to bind to the outside of cells (e.g., immune system cells) and induce biochemical changes in them [ 10 , 42 – 45 ].

In view of the visco’s ability to stimulate the immune system, it was classified as a type of biological response modifier [ 42 ]. Biological response modifiers constitute a diverse group of biological molecules that have been used individually, or in combination with other agents, to treat cancer or to lessen the side effects of anticancer drugs. Viscum extracts have been demonstrated in preclinical environments to have other mechanisms of action, such as antiangiogenesis [ 29 ].

Preparations from Viscum extracts are most often used in the treatment of cancer patients in German-speaking countries [ 46 ].

Commercially available extracts are marketed under a variety of brands including Iscador, Eurixor, Helixor, Isorel, Iscucina, planosol and abnobaVISCUM. Some extracts are marketed under more than one name. Iscador, Isorel and Planosol are also sold as Iscar, Vysorel and Lektinol, respectively. All these products are prepared from the Album Viscum (Loranthaceae – Viscum album L. or European Viscum).

In addition to the European Viscum, extracts of a type of Korean mistletoe ( Viscum album var. Coloratum [Kom.] Ohwi) demonstrated cytotoxicity in vitro and in vivo in laboratory studies. [ 47 – 51 ].

Viscum grows on various types of trees, and the chemical composition of extracts derived from it depends on the species of the host tree (e.g., apple, elm, oak, pine, poplar and fir), the time of year harvested, as the extracts are prepared, and the commercial producer. [ 8 , 43 , 52 – 55 ].

Viscum extracts are prepared as aqueous solutions or water and alcohol solutions, and can be fermented or unfermented [ 4 , 6 , 22 , 52 , 53 , 56 – 59 ]. Some extracts are prepared according to homeopathic principles, and others are not. Thus, like homeopathic preparations, they are usually not chemically standardized extracts [ 10 , 60 ]. In addition, commercial products can be subdivided according to the host tree species, which is typically indicated in the product name by a suffix letter. Iscador, a fermented aqueous extract from Viscum album L. that is prepared as a homeopathic drug, is marketed as IscadorM (from apple trees; Malus domestica ), IscadorP (of pine trees; Pinus sylvestris ), IscadorQu (oak; Quercus robur ) and IscadorU (elm; Ulmus minor). Helixor, an unfermented aqueous extract of Viscum album L. that is standardized for its biological effect on human leukemia cells in vitro,is marketed as HelixorA (from fir trees: Picea abies), HelixorM (from apple trees) and HelixorP (pine) [ 57]. Eurixor (which is no longer available on the market for sale), an unfermented aqueous extract from viscum album L., harvested from alamos, is standardized to contain a specific amount of one of the Viscum lectins. (lectin ML-1) [ 57 ]. Some proponents claim that the choice of extract should depend on the type of tumor and the sex of the patient [ 55 , 57 61 and 62 ].

Viscum extracts are generally given by subcutaneous injection, although administration by other routes (e.g., oral, intrapleural, intratumoral and intravenous) has been described [ 19 , 22 – 26 , 39 , 43 , 55 , 57 , 60 , 64 – 70 ]. In most of the reported studies, subcutaneous injections were administered 2 to 3 times a week, but the total duration of treatment varied considerably.



Viscum album and leukemias

It has been demonstrated for the first time that solubilized triterpenes or lectins and their combinations induce dose apoptosis and dependent time on the ALL NALM-6 cell line. Based on in vivo data, the authors concluded that triterpenes containing extracts from Viscum album L. may have an impressive therapeutic potential [71]:

In addition, it has been investigated whether extracts containing triterpenes may also induce dose-dependent apoptosis in primary cells of patients with ex vivo infantile leukemia. Here, we also observed the induction of apoptosis, via the caspase-8 and -9 signaling pathways, for viscum, TT and viscumTT.

Mice with leukemia were treated with extracts of Viscum album L. Receptors that received PBS had an average survival time of 38 days, while viscumTprolonged the average survival to 50.5 days. Together, the authors showed that this new formulation “viscumTT” of aqueous extracts of Viscum and triterpenic acids can induce apoptosis in intrinsic ally and extrinsic leukemia cells. In addition, a synergistic effect was revealed for the viscumTT combination compared to single-fraction viscum and TT. Based on these data, the authors believe that the extracts of Viscum album L. have excellent anticancer potential [72]:

Combined treatment of leukemia cells led to an inhibiting synergism in sub apoptotic concentrations of doxorubicin and multiform reduction of cytotoxic effects in healthy control cells. Co-treatment with prolonged Viscum album was associated with reduced G2/M accumulation and increased expression of early and late apoptotic markers. The authors concluded that Viscum album increases the antileamica efficacy of doxorubicin against k562 resistant cells by preventing G2/M arrest and inducing apoptosis [73]:

In Germany, 58.4% of cancer patients use complementary therapies, of which 61.6% use Viscum album – according to a cross-sectional multicenter study conducted in several hospitals (Weis et al., 1998). In this country, Helixor is the third most prescribed cytostatic drug on an outpatient basis (Schwabe & Paffrath, 2007).

Patients with chronic myeloid leukemia (N=30) had prolonged median survival by the addition of Helixor to Bussulfan (55.7 months versus 30 months of the historical control group with comparable prognostic factors, treated only with Bussulfan) (Gutsch, 1982).

The efficacy of adjuvant treatment with Helixor in lymphoma and chronic leukemia was analyzed in a retrospective study with 700 patients (Stumpf et al., 2000): additional treatment with Viscum album resulted in increased median survival (11.4 years versus 8.6 years for patients without Viscum). In addition, patients reported improvement in quality of life. The theoretical objection on unfavourable impacts of the use of Viscum in malignant neoplasms of the lymphatic and hematopoietic system is refuted by this study [74].

Acute myeloid leukemia (AML) is the second most common type of leukemia in the U.S. and Germany. The incidence increases with age and less than 10% of patients are children. The additional use of viscumTt strongly enhances the anti-tumor effect of cytarabine. In summary, the authors demonstrated that viscumTextract combining aqueous Viscum compounds and triterpenic acids induces apoptosis in HL-60 cells through intrinsic and extrinsic signaling pathways. The in vivo study showed a strong therapeutic effect for viscumT comparable to that of cytarabine. The potentiating effect of viscumTt and cytarabine provides strong evidence of combination with classical chemotherapy agents to achieve a high synergism of efficacy in cancer treatment [75]:



Other potential uses for the Viscum album

Among the well-described and most active phytochemicals identified in the Viscum album are lectins and viscotoxins, which play a substantial role in the treatment of cancer because of its apoptotic and cytotoxic effects. Another group of compounds found in Viscum album are phenolic acids, phenylpropanoids and flavonoids with antioxidant and anti-inflammatory activities, which lower blood pressure. Other components of Viscum include triterpenes with cytotoxic and apoptotic and phytosterol, oligo and polysaccharide properties. Plant extracts, especially aqueous, are applied in traditional and official medicine, among others in the treatment of hypertension or arthritis. Potentially, it can also be used as a hepatoprotective or sedative medicine[76]:

Extracts of Viscum album L and lectins isolated from Vicum have immunostimulant properties and a strong dose-dependent cytotoxic activity. They are often used in complementary cancer treatment, primarily to improve quality of life[77]:




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