Омела белая Viscum album Mistletoe

3.2. Morphological Bioassay

The significant main effect for the independent parameter experiment number is due to the variations in absolute values of the outcome parameter root/shoot-ratio, which were most probably due to (i) the variations in colchicine concentration (17, 18, and 20 μg/mL) and (ii) differences in room temperature between the seven independent experiments.

The significant main effect for the independent parameter treatment reveals the impact of the mistletoe extracts on the root/shoot-ratio of Lepidium sativum seedlings (Figure 4(a)); the LSD test differentiates the effects of the treatments water control, VAE, and APVAE (P < 0.001 for all pairwise comparisons). No significant difference in the root/shoot-ratio of Lepidium sativum seedlings was observed regarding mistletoe host tree (Malus versus Pinus, cf. Figure 4(a)).

4. Discussion

In contrast, comparably large and highly significant differences between anthroposophically processed and unprocessed mistletoe extracts (APVAE versus VAE) were observed in the morphological bioassay with Lepidium sativum. The formation of the so-called colchicine tumors was reduced by application of VAE, and this reduction of tumor formation was enforced by APVAE, as depicted by the changes in the root/shoot-ratio being correlated to the formation of colchicine tumors. Furthermore, this decrease in tumor formation was comparable for extracts from mistletoe growing on the host trees apple and pine (VAE/APVAE Mali and Pini, resp.). VAE/APVAE Pini has only very low concentrations of mistletoe lectins, and concentration and composition of viscotoxins differ to a large extent between apple and pine mistletoe extracts [27]. Thus, neither mistletoe lectins nor viscotoxins can be the cause for the observed reduction in colchicine tumor formation.

In plants, colchicine inhibits microtubule assembly by binding to the dimeric subunit of the microtubule, tubulin [28]. This leads to reduction of cell polarity and—in dividing cells—also to polyploidy [29, 30], with the consequent formation of colchicine tumors, consisting of malformed cells or cell assemblies [31]. An interference of some compound(s) present in mistletoe extracts with the tubulin-colchicine reaction is in principle conceivable; we currently have no hypothesis which substance(s) might be responsible for any such interference, however. According to the results obtained and discussed above, mistletoe lectins and viscotoxins most probably have to be excluded as possible candidates for such interference.

The results of the present study are in line with an earlier investigation of colchicine tumor formation in Triticum aestivum shoots treated with VAE and APVAE Mali: an analogous reduction of tumor development through application of VAE Mali and an additional decrease of tumor incidence through application of APVAE Mali were observed [32]. Similarly, crown-gall-tumor formation in Kalanchoe daigremontiana induced by Agrobacterium tumefaciens was reduced through application of VAE Mali; this decrease was further enforced after application of APVAE Mali [24]. Furthermore, damage induced by ultraviolet radiation (UV) on Triticum aestivum shoots as well as Sinapis alba shoots could be alleviated after application of VAE and APVAE Mali, but with stronger effects of APVAE compared to VAE [32].

Summarizing, effects of the anthroposophic pharmaceutical process in question were observed in five different whole system bioassays (colchicine tumor formation in Lepidium sativum, colchicine tumor formation in Triticum aestivum, crown-gall-tumor formation in Kalanchoe daigremontiana, UV damage in Triticum aestivum, and UV damage in Sinapis alba). In all five bioassays, anthroposophically processed Viscum album extracts (APVAE) induced a stronger morphostatic protection effect than unprocessed Viscum album extract (VAE). In contrast, no unambiguous effects of the investigated anthroposophic pharmaceutical process were observed regarding toxicity of Viscum album extracts in seven cancer cell lines (NCI-H460, DU-145, HCC1143, MV3, PA-TU-8902, Molt4, and Yoshida) of different origins (pancreas adenocarcinoma, metastatic melanoma, prostate, breast, and lung carcinoma, leukemia, and sarcoma).

This means that the high-speed blending process of summer and winter mistletoe extracts seems to induce some specific properties in Viscum album extracts that support morphostasis, that is, that help entire organisms to maintain their organization and form when threatened by noxious external factors. In contrast, no clear effect of the blending process was observed on lectin- and viscotoxin-based toxicity against cancer cell lines. Thus, it seems that preclinical methods derivable from the basic structure of the tissue organization field theory (TOFT) of cancer are more apt to investigate the anthroposophic pharmaceutical process in question, compared to preclinical methods derived from the somatic mutation theory (SMT) of cancer.

Anthroposophically processed Viscum album extracts from the host tree pine (APVAE Pini) led to a stabilization of the DNA of amniotic fluid cells in vitro [33]. Furthermore, APVAE Mali led to an improvement of DNA repair in gamma-ray or 4-hydroxycyclophosphamide damaged peripheral blood mononuclear cells (PBMC) in vitro [34]. A similar protection effect of APVAE Pini in PBMC poisoned with 4-hydroxycyclophosphamide was observed in a follow-up in vitro study, alongside the absence of any such protection effect in malignant Jurkat cells [35]. None of these three investigations was able to identify possible compounds of the mistletoe extracts that might be responsible for this DNA stabilizing effect.

In animal trials, anthroposophically processed Viscum album extracts exerted protective effects against carcinogenic compounds (N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide, 20-methylcholanthrene) in trials with rats and mice [36, 37]. Furthermore, treatment with APVAE Mali resulted in a faster recovery from radiation- or cyclophosphamide-induced leukopenia in mice [38].

The results of the abovementioned preclinical investigations are in line with observations made in clinical trials. Kovacs et al. observed that DNA repair in lymphocytes of breast cancer patients could be substantially improved after subcutaneous injections of APVAE Mali [39]. Furthermore, there are several clinical investigations that documented a reduction of side effects of conventional antitumor therapy by simultaneous APVAE therapy, without reducing the former's efficacy [40–43].

Taken together, these preclinical and clinical observations support the hypothesis that the application of APVAE may help organisms (cells, plants, animals, and humans) in their continuing quest for maintenance of organization and form, especially when endangered by external noxious influences or by endogenous tumor formation. In addition, based on the results of the present and earlier investigations [24, 32], we put forward the hypothesis that part of the effects of APVAE is due to the specific anthroposophic pharmaceutical processing applied.