A new development of triterpene acid‐containing extracts from <i>Viscum album</i> L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia

Delebinski, Catharina I.; Jaeger, Sebastian; Kemnitz-Hassanin, Kristin; Henze, Günter; Lode, Holger N.; Seifert, Georg

doi:10.1111/j.1365-2184.2011.00801.x

Cited by 37 publications

(61 citation statements)

References 62 publications

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“…22,25,26 In vitro studies have shown induction of apoptosis and necrosis depending on mistletoe extract concentrations in a wide range of tumor cells. [19][20][21]25,27,28 Preclinical in vivo studies have likewise been promising, with IT injection of tumors in a range of mice models and in horses inhibiting tumor growth and inducing partial or complete regressions. 25,26,28,29 As for clinical use, several groups have published case studies describing partial or complete tumor remission by IT mistletoe therapy alone or in combination with conventional therapies.…”

Section: Introductionmentioning

confidence: 99%

“…10,[13][14][15][16][17] A major challenge of cancer therapy is immune resistance orchestrated by the tumor microenvironment, which promotes tumor survival. 18 European mistletoe (Viscum album [19][20][21][22] Used in anticancer therapy in central Europe since 1917, anthroposophic mistletoe preparations (ie, Abnoba viscum, Helixor, Iscador, Iscucin, Isorel) are usually injected subcutaneously (SC), as an adjuvant therapy to conventional cancer treatments. The aims of SC-injected mistletoe (also intravenous [IV]), are to boost the immune system, improve patient health-related quality of life, and reduce ADRs associated with conventional therapies.…”

Section: Introductionmentioning

confidence: 99%

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Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L) Preparations in Oncology

et al. 2014

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Background. Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed. Methods. The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors. Results. A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin).The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively. Conclusion. IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might be critical for tumor response. In light of these results, IT mistletoe therapy seems to be safe and prospective trials are recommended.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L) Preparations in Oncology

et al. 2014

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“…In German-speaking countries, there is a high prevalence of complementary and alternative medicine, 41,42 and European mistletoe extracts (Viscum album L.) are the mostly frequently prescribed herbal remedies. [43][44][45][46][47][48] An overview on the mode of action of mistletoe extracts is given by Bar-Sela 49 and has been well summarized by Zänker et al 50 In vitro, it showed antitumoral effects, such as induction of apoptosis, [44][45][46][47][48]51 inhibition of cell proliferation, 47,48,52 potentiating anticancer effects of TNF-alpha, 53,54 activation of immunocompetent cells, [54][55][56][57] decreasing angiogenesis, 50,53 and retention of chemotherapeutic agents in cancer cells by modulating the transport of cell-toxifying substances. 58 Whereas systemic mistletoe therapy primary aims to stimulate the immune system, intratumoral application focuses on the local cytotoxic effect.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral Mistletoe (Viscum album L) Therapy in Patients With Unresectable Pancreas Carcinoma

et al. 2013

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Pancreatic carcinoma remains one of the main causes for cancer-related death. Intratumoral application of anticancer agents is discussed as a promising method for solid tumors such as pancreatic cancer. Endoscopic ultrasound provides a good tool to examine and treat the pancreas. European mistletoe (Viscum album L) is a phytotherapeutic commonly used in integrative oncology in Central Europe. Its complementary use seeks to induce immunostimulation and antitumoral effects as well as alleviate chemotherapeutic side effects. Intratumoral mistletoe application has induced local tumor response in various cancer entities. This off-label use needs to be validated carefully in terms of safety and benefits. Here we report on 39 patients with advanced, inoperable pancreatic cancer, who received in total 223 intratumoral applications of mistletoe, endoscopic ultrasound guided or under transabdominal ultrasound control. No severe procedure-related events were reported. Adverse drug reactions were mainly increased body temperature or fever in 14% and 11% of the applications, respectively. Other adverse drug reactions, such as pain or nausea, occurred in less than 7% of the procedures. No severe adverse drug reaction was recorded. Patients received standard first-and second-line chemotherapy and underwent adequate palliative surgical interventions as well as additive subcutaneous and partly intravenous mistletoe application. A median survival of 11 months was observed for all patients, or 11.8 and 8.3 months for stages III and IV, respectively. Due to the multimodal therapeutic setting and the lack of a control group, the effect of intratumoral mistletoe administration alone remains unclear. This retrospective analysis suggests that intratumoral-applicated mistletoe might contribute to improve survival of patients with pancreatic cancer. In conclusion, the application is feasible and safe, and its efficacy should be evaluated in a randomized controlled trial.

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“…Mistletoe is grown on different host trees such apple, pine, oak, fur, maple, poplar, or hawthorn. 23 In Europe, mistletoe lectin has been widely used as a complementary cancer drug for various cancers, such as gliomas, 24 acute lymphoblastic leukemia, 25 breast cancer, 26 sarcoma, 27 and others. 28 However, there has been no study showing the anticancer activity of mistletoe alkali.…”

Section: Ge Effects Of Mistletoe Alkali On Human Osteosarcoma Cells (mentioning

confidence: 99%

Proliferation, Apoptosis, and Invasion Effects of Mistletoe Alkali on Human Osteosarcoma U2OS In Vitro

Wang

Pang

et al. 2016

International Surgery

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The objective of this study was to evaluate the effects of mistletoe alkali on human osteosarcoma cells (U2OS) in vitro. Osteosarcoma is the most common primary malignant bone tumor; although there are a lot of therapies such as surgery, radiotherapy, and chemotherapy, its prognosis is still very poor. There is increasing interest in the protective biological function of natural antioxidants contained in Chinese medicinal herbs, which are candidates for the prevention of tumors. Mistletoe alkali is one of the compounds extracted from Viscum coloratum (Komar.) Nakai, one kind of mistletoe, whose extracts contribute to the improvement of the prognosis of patients with malignancies. The effect of mistletoe alkali on the growth of U2OS cells was compared with 5-fluorouracil (5-FU), using a cell counting kit-8 (CCK-8). The influence of mistletoe alkali on U2OS's proliferation and apoptosis was tested by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling staining and immunocytochemical staining of caspase 3 and proliferating cell nuclear antigen. Additionally, the invasion ability of U2OS cells was detected using a Boyden chamber transwell migration assay. CCK-8 assays gave an IC50 of 7 μg/mL for mistletoe alkali. Compared with 5-FU, mistletoe alkali inhibited U2OS proliferation and induced apoptosis more effectively. The invasion ability of U2OS was also weaker in mistletoe alkali than in 5-FU. Mistletoe alkali significantly inhibited growth and invasion abilities of U2OS cells and induced their apoptosis in vitro. Mistletoe alkali may be a more effective drug for human osteosarcoma than the standard chemotherapeutic drug 5-FU.

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A new development of triterpene acid‐containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia

Abstract: Here for the first time, we have demonstrated that either solubilized triterpene acids or lectins and combinations thereof, induce dose-dependent apoptosis in the ALL cell line NALM-6 via caspase-8 and -9 dependent pathways.

Cited by 37 publications

References 62 publications

Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L) Preparations in Oncology

Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L) Preparations in Oncology

Intratumoral Mistletoe (Viscum album L) Therapy in Patients With Unresectable Pancreas Carcinoma

Proliferation, Apoptosis, and Invasion Effects of Mistletoe Alkali on Human Osteosarcoma U2OS In Vitro

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