The immune-system–stimulating and cytotoxic properties of mistletoe have both been investigated in laboratory and animal studies.

Laboratory studies have shown that mistletoe extracts can stimulate the activity of white blood cells in vitro and cause them to release molecules thought to be important for anticancer immune responses.[1-10] Reviewed in [11-18] In addition, mistletoe extracts have demonstrated cytotoxic activity against a variety of mouse, rat, and human cancer cells in vitro.[19-36] Reviewed in [12,37,38] In one study, however, the in vitro growth of several types of human cancer cells was stimulated by treatment with low doses of the purified lectin ML-I.[32]

Studies of the ability of mistletoe to inhibit cancer cell growth in animals have yielded mixed and inconsistent results.[20,24,26,30,39-42,18,43-45,36] Reviewed in [12,38,15,46] In most of these studies, mistletoe extracts were administered either by subcutaneous injection or by intraperitoneal injection.

In one animal study, treatment with IscadorM increased the survival time of mice that had been implanted with one type of mouse cancer cell (Ehrlich ascites) but not 2 others (L1210 leukemia; B16 melanoma).[20] The effect of IscadorM on the growth of tumors formed in mice by 3 additional types of mouse cancer cells (Lewis lung carcinoma; colon adenocarcinoma 38; C3H mammary adenocarcinoma) was also assessed in this study. Treatment with IscadorM substantially reduced the growth rate of all 3 types of tumors.

In another animal study, mice were given IscadorM before, during, or after injection with either of 2 types of mouse cancer cells (Dalton’s lymphoma; Ehrlich ascites).[26] In this study, all groups of mice treated with mistletoe showed substantially slower tumor growth than the control groups.

In contrast, no antitumor effect or improvement in survival was observed when IscadorM was used to treat rats bearing chemically induced mammary carcinomas or tumors formed from rat Walker 256 carcinosarcoma cells.[44] In this study, IscadorM was also not effective in treating mice that had been injected with Ehrlich ascites cells. In addition, IscadorP was found ineffective in treating rats with tumors formed from rat L5222 leukemia cells.

Treatment with the mistletoe extract Lektinol (also sold as Plenosol; see General Information section) has likewise yielded mixed results in animal experiments.[43] Treatment with Lektinol slowed the growth of tumors formed in mice from implants of 3 types of mouse cancer (colon adenocarcinoma 38; Renca renal cell carcinoma; F9 testicular carcinoma) but not 2 others (B16 melanoma; Lewis lung carcinoma).

The anticancer effects of Isorel (also sold as Vysorel; see General Information section) have been examined in at least 2 animal studies.[30,36] In one study, IsorelM was used alone or in combination with local x-ray therapy in mice bearing mouse CMC-2 fibrosarcoma tumors.[30] When IsorelM was used alone, no effect on either tumor growth or animal survival was observed. However, when IsorelM injections were combined with local x-ray therapy of tumors, substantial improvements in survival were found in comparison to the survival of mice treated with local x-ray therapy alone. With local x-ray therapy alone, 22% of mice were cured of their tumors. When local x-ray therapy was combined with IsorelM injections, given before or after the x-ray treatment, the cure rate increased to 43%. When IsorelM was given both before and after local x-ray therapy, the proportion of cured mice increased to 67%.

In another study, IsorelM showed antitumor and antimetastatic effects in mice that had been injected with mouse mammary carcinoma cells.[36] The antitumor effects appeared most pronounced when IsorelM was injected in the vicinity of tumors.

The ability of purified or recombinant lectin ML-I to inhibit the formation of chemically induced bladder tumors in rats has been evaluated in 3 studies.[41,42,45] Reviewed in [12] In 2 of the studies, purified ML-I was given by subcutaneous injection.[41,42] Reviewed in [12] Treatment with ML-I did not reduce the frequency of bladder tumor formation or increase immune system activity in the bladder wall in either study. In the third study, recombinant ML-I was introduced directly into the bladder through a process known as intravesical instillation.[45] Reviewed in [12] In this study, the frequency of bladder tumor formation was reduced by approximately 50% in ML-I-treated animals. However, as in the other 2 studies, immune system activity in the bladder wall was not increased substantially. It was concluded, therefore, that the antitumor effect observed in this study was the result of direct cytotoxic action by the recombinant lectin against malignant cells.[45]

Finally, a few animal studies have suggested that mistletoe is beneficial in decreasing the side effects of conventional anticancer therapy (e.g., chemotherapy and radiation therapy) and that it counteracts the effects of drugs used to suppress the immune system.[47-49] Reviewed in [38] In one study, IscadorM was shown to increase the number of white blood cells in mice treated with cyclophosphamide chemotherapy or radiation therapy and to decrease the amount of weight loss due to radiation, but not cyclophosphamide, treatment.[49] Recombinant mistletoe lectin has also been shown to induce increased apoptosis when combined with x-ray treatment.[50] In another study, IscadorM was shown to accelerate the recovery of hematopoietic tissue in the bone marrow and spleens of irradiated rats and mice.[47] In yet another study, the mistletoe product Eurixor was shown to counteract the immunosuppressive effects of treatment with the drug cortisone.[48]

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