Mistletoe-Based Drugs Work in Synergy with Radio-Chemotherapy in the Treatment of GliomaIn VitroandIn Vivoin Glioblastoma Bearing Mice

Abstract

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.

Effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer: a cohort study

“…Sabová et al studied the cytotoxic and apoptotic effects of mistletoe extract in combination with doxorubicin on Jurkat cells and observed a dose-dependent DNA fragmentation [ 34 ]. Schötterl et al, using in vitro and in vivo assays, investigated the synergistic effect of mistletoe-based drugs with TMZ-based chemoradiation in the treatment of glioblastoma [ 35 ]. The combined treatment showed additive effects in reducing the survival of the tested tumor cell lines in clonogenic assays.…”

An Extract of Transgenic Senna obtusifolia L. hairy roots with Overexpression of PgSS1 Gene in Combination with Chemotherapeutic Agent Induces Apoptosis in the Leukemia Cell Line

“…Previous studies have so far addressed only the cytotoxic effect of Senna spp. extracts derived from wild, ex vitro, untransformed plants: Despande et al [47] report that stem extract of S. obtusifolia, S. glauca and S. sophera exhibited cytotoxic effects against breast cancer cell lines, while others report cytotoxic effects following treatment with S. nigricans on MCF-7 (adenocarcinoma estrogen-responsive breast cancer) and S. alata extracts on A549 (epithelial human lung adenocarcinoma cancer) cell lines [48][49][50].…”

The Anti-Inflammatory Activity of Viscum album

“…During the last years, the antitumor activity of V. album preparations has been reported and checked in many clinical reports from 1919, with potential effectiveness in the treatment of neuroblastoma [ 98 ] and other cancer cases [ 99 , 100 ]. Viscum preparation was used in clinical combined therapy of advanced metastatic cancers [ 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ], whose effects were mainly attributed to viscotoxins and viscolectins.…”