engleski

An overview of anticancer phytotherapy using Viscum album extract Isorel: Novel findings of simultaneous anticancer and anti-diabetic effects in mice bearing solid form of Ehrlich Ascytic Tumor

Current approaches in combined therapy of cancer include chemotherapy protocols which aim to induce the death of cancer cells and spare non-malignant cells. Gene therapy and intelligent drug delivery systems should assure either selective cytotoxicity for cancer cells or adjustment of the growth control of cancer cells in directon of its regression in particular through apoptosis. Modern complementary medicine tends to combine convential therapies with scientifically validated traditional medical treatments that should increase the resistence of the organism to cancer and in parallel reduce the growth capacities of cancer cells. Hence, combined approaches in complex therapy of cancer tend to cure the organism not just to destroy the cancer cells. However, the therapies used sometimes cannot have insight in the overall health status of the organism, i.e. presence of other diseases. This can cause undesirable side effects or, on the contrary, unusual phenomena of healing. This happens often in patients that practice additional treatments based on natural drugs, mostly plant extracts, in particular if they are able to modulate cell growth, metabolism, immune system function and oxidative stress. Because mistletoe (Viscum album) has such activities it has a long history of plant source for the preparation of different medical extracts. Various types of mistletoe (not just the most popular “ European Viscum album” ) have been used worldwide for different diseases, such as hypertension, diabetes mellitus, pain syndromes, auto-immune diseases, etc. Most of these therapies are not based on scientific data, but empirical findings obtained from peroral use of different plant preparations. On the contrary, scientifically validated aqueous Viscum album drugs are given almost exclusively to cancer patients s.c., i.m. or i.v. in adjuvant therapies. Several data point to a cytotoxic action of these extracts against various tumor cell lines, while their in vitro toxicity for normal cells is less pronounced, indicating relatively selective toxicity primarily against the tumor cells. On the other hand, the application of Viscum album extracts in vivo might have immunomodulating effects, mainly stimulating cytotoxic activity of the lymphocytes. The dual activity of mistletoe preparations, i.e. cytotoxicity for the tumor cells and the enhancement of the immune host defense against the malignant cells, gives a support for the practical use of these preparations in human medicine. We used the Viscum album drug Isorel (Novipharm, Austria) for 17 years in preclinical studies that revealed anticancer effects of the drug in particular if used together with radio- or chemotherapy. Isorel attenuates in vitro cytotoxicity of Cyclophosphamide for normal lymphocytes while in vivo it increases efficiency of Cyclophosphamide against experimental metastasis of murine mammary carcinoma. Moreover, combined postoperative chemotherapy and i.v. Isorel biotherapy, either adjuvant or palliative, resulted in increased survival of patients with advanced colorectal carcinomas. Similarly, perioperative s.c. use of the drug in cancer patients revealed its efficiency in immune stimulation and improved recovery of patients. Because cancer often develops in patients suffering from other severe diseases while some patients cannot use the drug given parenterally as recommended, we made a pilot study on the effects of the drug given per os to diabetic mice (Aloxan pretreated) bearing EAT in the hind limb.The growth of the tumors was inhibited in diabetic tumor bearing mice consuming Isorel from the sixth week after tumor transplantation, when all the mice from the control diabetic-tumor bearing group were already dead, i.e. at the time when the inhibition of the tumor growth was also observed for the non-diabetic mice treated with Isorel. The use of Isorel markedly attenuated also polydipsia, polyuria, glucosuria and the loose of the body weight (hyperglycemia could not be monitored). Finally, comparison of the individual pattern of the tumor growth and the severity of diabetes mellitus revealed that four animals without glucosuria lived much longer than the other animals from the same or the control group. Thus, the disappearance of the symptoms of diabetes in Isorel treated mice was associated with the inhibition of the tumor growth and the extension of the survival duration, too.

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