engleski

Biological effects of the Viscum album extract Isorel: overview on some general findings and recent experiments on the interference of plasma and tumor cells' lysates with antitumorous activity of the drug in vitro

Studies performed during last ten years revealed that mistletoe extract Isorel (Novipharm GmbH, Austria) inhibits in vitro growth of various human and animal malignant cell lines. It appears that for the lectin-like activity of the drug not only mistletoe lectins, but also certain low molecular weight components are responsible. Treatments with Isorel reduced in vivo growth of solid murine tumors as well as development of artificial lung metastases, increasing effectiveness of radiotherapy or chemotherapy. Moreover, mistletoe extract influenced tumor:host relationship modulating inflammatory response and increasing onsets of both apoptosis and necrosis in the affected tumor tissue in particular at the site of the extract application. Hence, possible mutual interactions of biological activities of mistletoe extracts with bioactive factors of the organism (pro- and anti-oxidative factors, cytokines, enzymes, etc.) might be relevant to understand activity principles of mistletoe cancer therapy. There are data indicating that antitumorous effects of mistletoe drugs depend on the activity of certain humoral (plasma) factors. On the other hand, it is not clear if the active components of the mistletoe drugs interfere with the products of the cellular necrosis, i.e. factors released during tumor decay. Hence, the aim of our recent experiments was to get some preliminary insight in a pos-sible influence of cellular lysis products and of plasma presence on the in vitro effects of Isorel. For this purpose we studied in vitro influence of the ultrasound-destroyed melanoma B16F10 cells (lysate) on the growth inhibition (upon the 3H-thymidine [3H-TdR] incorporation) of the same type of malignant cells caused by plasma-interfering activity of the drug. Cellular lysate decreased the 3H-TdR incorporation in the absence of plasma, except if the cells were pre-cultured with the plant extract in plasma supplemented medium. Plasma supplementation reduced the inhibiting effects of the lysate only for the cells that were pre-cultured without plasma, while in the presence of plasma the lysate reduced 3H-TdR incorporation in the cells pre-cultured with Isorel in plasma supplemented medium (those otherwise not sensitive to the inhibiting effects of the lysate). Even more, although plasma itself did not have significant impact on the growth of the cells pre-cultured without Isorel, it stimulated the growth of the cells pre-cultured with Isorel, but only for the cells pre-cultured with the extract in the absence of plasma. Pre-culturing the cells with the extract in the absence of plasma reduced their growth capacity for more than 70% below control, while plasma increased their viability and made them not only insensitive to the growth promoting effect of plasma, but also to the growth inhibiting effects of the cellular lysate. Irrespective of the parameters of pre-culturing, incubating cells with 1% Isorel almost completely abolished the 3H-TdR incorporation. Human plasma strongly reduced inhibition of the 3H-TdR incorporation caused by Isorel, while the lysate used without plasma did not influence the growth inhibiting activity of the plant extract. Finally, combined treatment with lysate 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. Thus, although it is uncertain if the cellular factors from the lysate interfere directly with the bioactive components of the plant extract, it is certain that mutual dependence of their biological activities increased antitumorous effects of Isorel "avoiding" cell-protective effects of plasma. The nature of these factors and their interactions with plasma and mistletoe components should be further studied.

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