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Planta Med 2019; 85(14/15): 1150-1159
DOI: 10.1055/a-1013-0382
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Preclinical Evaluation of Antitumoral and Cytotoxic Properties of Viscum album Fraxini Extract on Pediatric Tumor Cells

Katrin Menke
1   Department of Pediatric Oncology and Hematology, University Childrenʼs Hospital Essen, Essen, Germany
,
Melanie Schwermer
1   Department of Pediatric Oncology and Hematology, University Childrenʼs Hospital Essen, Essen, Germany
2   Department of Pediatric and Adolescent Medicine, Gemeinschaftskrankenhaus Herdecke, Herdecke, Germany
,
Alexander Schramm
3   Molecular Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
,
Tycho J. Zuzak
1   Department of Pediatric Oncology and Hematology, University Childrenʼs Hospital Essen, Essen, Germany
2   Department of Pediatric and Adolescent Medicine, Gemeinschaftskrankenhaus Herdecke, Herdecke, Germany
› Author Affiliations
Further Information

Publication History

received 06 April 2019
revised 12 September 2019

accepted 12 September 2019

Publication Date:
07 October 2019 (online)

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Abstract

In Europe, especially in German-speaking countries, administration of mistletoe extracts is the most common and popular complementary and alternative therapy approach reported in oncology. Mistletoe therapy is applied to children with cancer for curative and palliative therapeutic regimes with increasing frequency, but at the same time, there are only a few studies on the effectiveness of this therapy. Therefore, we have investigated the response of various pediatric cell lines (acute myeloid leukemia, Ewingʼs sarcoma, hepatocellular carcinoma, medulloblastoma, neuroblastoma, and osteosarcoma) to mistletoe extract, abnobaVISCUM Fraxini. Effects on cell proliferation, cell cycle distribution as well as on mitochondrial integrity and caspase-mediated apoptosis were investigated in neuroblastoma cell lines, SH-SY5Y and Kelly. Additionally, in vitro tumor cell migration and invasion were studied. In vivo effects of the mistletoe extract were investigated in a syngeneic neuroblastoma mouse model. We could show that tumor cell lines were from 5- to 640-fold more sensitive to abnobaVISCUM Fraxini treatment than non-tumorigenic fibroblasts, whereby neuroblastoma cell lines were the most sensitive. For two neuroblastoma cell lines, SH-SY5Y and Kelly, induction of caspase-9-mediated apoptosis, a decrease of mitochondrial integrity as well as attenuation of migration and invasion were observed. In vivo experiments revealed a reduction of tumor growth and a prolonged survival of tumor-bearing animals. In summary, we can state that these results provide the first preclinical data for cytotoxic activities of abnobaVISCUM Fraxini for a broad panel of pediatric tumor cell lines, in particular, neuroblastoma cells. Thus, it might be a potential remedy for the supportive treatment of neuroblastoma.

Key words

pediatric oncology - phytotherapy - mistletoe - Viscum album - Santalaceae - neuroblastoma

Supporting Information

    Further experiment data investigating the apoptosis pathway are provided in Supporting Information (Figs. 1S and 2S). Upregulation of CASP9 expression in SH-SY5Y and Kelly cells after aVF treatment were demonstrated by qRT-PCR (Fig. 1S). Supplemental data of the rescue experiment with the pan caspase inhibitor, Q-VD-OPh, showing distribution of cell cycle phases elicit an induction of G2-phase cells after inhibiting apoptosis (Fig. 2S). Additional data for in vivo experiments are provided in Figs. 3S and 4S. Here, IC50 of the used murine neuroblastoma cell line, C1300, are demonstrated. Body temperature curve indicating possible inflammation reactions of aVF i. p.-treated mice is shown in Fig. 4S.

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