Mistletoe-based drugs work in synergy with radio-chemotherapy in the treatment of glioma in vitro and in vivo in glioblastoma bearing mice

Background. Extracts from Viscum album L. (VE) are used in the complementary cancer therapy in Europe for decades. VE contain several compounds like the mistletoe lectins (MLs) 1-3 and viscotoxins and also several minor 
Background. Extracts from Viscum album L. (VE) are used in the complementary cancer therapy in Europe for decades. VE contain several compounds like the mistletoe lectins (MLs) 1-3 and viscotoxins and also several minor ingredients. Since mistletoe lectin 1 (ML-1) has been described as the main component of VE harboring antitumor activity, purified native or recombinant ML-1 has been recently used in clinical trials. MLs stimulate the immune system, induce cytotoxicity, are able to modify the expression of cancer-associated genes, and influence the proliferation and motility of tumor cells.
Objective. In this study our goal was to determine anticancer effects of the VE ISCADOR Qu, of recombinant ML-1 (Aviscumine), and of native ML-1 in the treatment of glioblastoma (GBM), the most common and highly malignant brain tumor in adults. Additionally we were interested whether these drugs, used in combination with a temozolomide-(TMZ)-based radio-chemotherapy, provide synergistic effects.
Methods. Cell culture assays, ex vivo murine hippocampal brain slice cultures, human GBM cryosections, and a xenograft orthotopic glioblastoma mouse model were used.
Results. In cells, the expression of the ML receptor CD75s, which is also expressed in GBM specimen, but not in normal brain, correlates with the drug-induced cytotoxicity. In GBM cells, the drugs induce cell death in a concentration-dependent manner and reduce cell growth by inducing cell cycle arrest in the G2/M phase. The cell cycle arrest was paralleled by modifications in the expression of cell cycle regulating genes. ML containing drugs, if combined with glioma standard therapy, provide synergistic and additive anticancer effects. Despite not reaching statistical significance, a single intratumoral application of Aviscumine prolonged the median survival of GBM mice longer than tumor irradiation. Moreover, intratumorally applied Aviscumine prolonged the survival of GBM-bearing mice if used in combination with irradiation and TMZ for further 6.5 days compared to the radio-chemotherapy.
Conclusion. Our results suggest that an adjuvant treatment of glioma patients with ML-containing drugs might be beneficial.
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Author:Sonja Schötterl, Jennifer T. Miemietz, Elena Ilin, Naita M. Wirsik, Ingrid Ehrlich, Andrea Gall, Stephan Huber, Hans Lentzen, Michel Guy André Mittelbronn, Ulrike Naumann
URN:urn:nbn:de:hebis:30:3-507464
DOI:http://dx.doi.org/10.1155/2019/1376140
ISSN:1741-4288
ISSN:1741-427X
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=31354846
Parent Title (English):Evidence-based complementary and alternative medicine
Publisher:Hindawi
Place of publication:New York, NY
Contributor(s):Konrad Urech
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/07/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/08/15
Volume:2019
Issue:Art. 1376140
Pagenumber:18
First Page:1
Last Page:17
Note:
Copyright © 2019 Sonja Schötterl et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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