engleski

Overview on preclinical research on Isorel

European mistletoe (Viscum album L.) has a long history of medical plant, which nowadays becomes acknowledged also by the leading authorities in oncology, such as U.S. National Cancer Institute, Bethesda and MD Anderson Center in Houston. This trend of expanding interest in the biomedical use of mistletoe is based on intensive research activities carried during last 20 years, mostly in Central Europe. Further progress could be obtained if preclinical research will be combined with required clinical trials. To evaluate activity principles of aqueous mistletoe extract Isorel® produced by Novipharm GmbH (Pörtschach, Austria) from the entire plant (planta tota) we studied its effects on human and murine malignant cell lines in vitro and on the murine tumors in vivo. It was found that Isorel could inhibit the growth of the malignant cells and increase effectiveness of radiotherapy and chemotherapy as well as it stimulates host defense against cancer cells and might modulate non-specific immunity. The activity of Isorel appeared to be "lectin-like", but fractionating Isorel into different molecular weight (MW) components revealed that none of the fractions was as efficient as the plain drug indicating "multifactorial" activity principle. In vitro Isorel showed concentration dependent inhibition of the cell growth (toxicity) determined by the incorporation of the 3H-labelled amino acids in the various cell lines. For the growth inhibition mostly higher MW components were responsible, while <500 MW components were less efficient. Moreover, active components of the drug interfere with the serum components and with the products of the cellular necrosis, i.e. factors released during tumor decay. Namely, combined treatment of malignant cells in vitro with the cellular lysates and Isorel in the presence of plasma resulted in stronger growth inhibiting effects than noticed for the cells treated only with the lysate or with the plant extract. We further analyzed the effects of drug application in vicinity of tumor (murine mammary carcinoma) and compared it with systemic effects. Isorel was applied only at the right side (in the limb distal from the tumor) and caused persistent and almost complete inhibition of the tumor growth for some animals, while anticancer effects were less pronounced on the contralateral side tumors. Histology revealed that Isorel treatment, both at the side of tumor and systemically, increased the incidence of apoptosis and necrosis in the tumors, while reduction of mitosis was noticed only for the tumors exposed to direct Isorel treatment. Finally, animals treated with Isorel had, on the average, three times less lung metastases than the controls. Thus, we conclude that both local and systemic effects of the application of Isorel could be of benefit for the tumor-bearing organism resulting in immunomodulation combined with tumor growth inhibition and reduction of metastases.

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Rad je kao pozvano predavanje prezentiran i na skupovima Isorel symposium održanim: - 07.09.2002., Konstanca, Rumunjska ; - 29.03.2003., Jaš, Rumunjska ; uz međunarodnu recenziju objavljen u Knjizi sažetaka.