An Assessment of Mistletoe-Based Drugs Work in Synergy with Radio-Chemotherapy in the Treatment of Glioma in vitro and in vivo in Glioblastoma Bearing Mice

Abstract

Extracts from the mistletoe plant Viscum album L. (VE) are used in the complementary cancer therapy in Europe for decades. VE contain several compounds like the mistletoe lectins (ML) 1-3 and viscotoxins (VT), but also several minor ingredients. ML-1 is suggested to be the main anti-tumor component of VE, VT induce cell death, and some minor compounds can strengthen the anti-tumor activity of ML-1. ML 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. In this study we determine the anti-tumor 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 brain tumor in adults. Additionally, we were determined whether a mistletoe-based therapy, if used as adjuvant treatment in combination with temozolomide(TMZ)-or irradiation, provide synergistic effects. The expression of the ML receptor CD75s, which is expressed in GBM specimen and cells, but not in the normal brain, correlates well with the drug-induced cytotoxicity. In GBM cells, the drugs induce cell death in a concentration-dependent manner, induce an arrest in the G2/M phase and provide synergistic and additive anti-tumor effects. A single intratumoral application of Aviscumine prolonged the survival of GBM mice longer than tumor irradiation and was even better if used in combination with radio-chemotherapy. This indicates that an adjuvant treatment of glioma patients with ML-containing drugs might be beneficial.