Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro

Seifert, Georg; Jesse, Patrick; Läengler, Alfred; Reindl, Tobias; Lüth, Maria; Lobitz, Stephan; Henze, Günter; Prokop, Aram; Lode, Holger N.

doi:10.1016/j.canlet.2008.01.036

Cited by 89 publications

(76 citation statements)

References 27 publications

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“…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%

“…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%

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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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“…Moreover, this lectin showed in vitro ability to alter cytokine gene expression in human colonic carcinoma [126] and IEC-6 rat intestinal epithelial cells [127]. Seifert et al [128] showed that mistletoe lectin was able to cause cytotoxicity to human acute lymphoblastic leukemia cells through activation of apoptosis. Also, the intraperitoneal administration of mistletoe lectin preparations improved the survival of mice injected with leukemia cells without any side effects.…”

Section: Plant Lectinsmentioning

confidence: 97%

“…Hernandez-Ledesma et al [138] reported that the amino acid sequence 23-31 is responsible for lunasin to target histones H3 and H4; the RGD motif for the internalization of lunasin into the cells and the polyaspartic acid tail for direct binding of lunasin to core histones thereby affecting mitosis and eventually leading to cell death. Galvez and de Lumen [139] first reported the biological property of [166,167] Induction of LC3-II generation, double-layer vesicle, BNIP3 and acidic vascular formation (Con A, 40 μg/ml and 20 mg/kg, in vitro and in vivo) [168] Apoptosis Mitochondrial depolarization (mistletoe extract, 60-250 μg/ml, in vitro; Polygonatum cyrtonema, 15 μg/ml, in vitro) [128,166,167] Cytochrome c release (Polygonatum cyrtonema, 15 μg/ml, in vitro) [ 167,168] Caspase activation (Clematis montana, 1 pM, in vitro; Sophora flavescens, 1 μg/ml, in vitro) [ 134,135] Decreased expression of NF-κB, X-linked inhibitor of apoptosis proteins, and Akt/kinase B; activation of TNF receptor 1 and caspase-8 (Korean mistletoe, 100 ng/ml, in vitro) [124] Degradation of the cytoskeletal protein gelsolin (Viscum album agglutinin-I 1 μg/ml, in vitro) [ 129] Increased expression of FasL and FADD proteins (Polygonatum odoratum, 25 μg/ml, in vitro) [ 133] BNIP3 BCL2/adenovirus E1B 19 kDa protein-interacting protein 3, FADD Fas-associated protein with death domain lunasin, formerly known as a soybean cDNA encoding small subunit peptide of 2S soy albumin. They showed that transfection of lunasin plasmid into murine hepatoma cancer cells, murine fibroblast cells, and human cancer cells arrested cell division, caused abnormal elongation of spindle fiber, chromosomal fragmentation, and cell lysis.…”

Section: Rgd-containing Peptide: Lunasinmentioning

confidence: 99%

The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells

Mejía

Dia

2010

Cancer Metastasis Rev

144

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The process of carcinogenesis is complex and not easy to eliminate. It includes the initial occurrence of genetic alterations which can lead to the inactivation of tumor-suppressor genes and further accumulation of genetic alterations during tumor progression. Looking for food and food components with biological properties, collectively called nutraceuticals, that can hinder such alterations and prevent the inactivation of tumor-suppressor genes is a very promising area for cancer prevention. Proteins and peptides are one group of nutraceuticals that show potential results in preventing the different stages of cancer including initiation, promotion, and progression. In this review, we summarized current knowledge on the use of nutraceutical proteins and peptides in cancer prevention and treatment. We focused on the role of plant protease inhibitors, lactoferrin and lactoferricin, shark cartilage, plant lectins, and lunasin in the apoptosis, angiogenesis, and metastasis of cancer cells. Also included are studies on bioavailability and clinical trials conducted on these promising proteins and peptides.

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“…Accordingly, several plant lectins have been widely studied and were found to possess different tumor suppressive activities that are associated with a potent anticancer response [25,28,31] . For example, mistletoe lectins belonging to the RIP II family have been shown to inhibit lymphoma growth in mice and are used as an adjuvant therapy to treat various forms of human cancers [40] . Therefore, the results of this study support the use of AGG as a naturally occurring anticancer molecule for liver cancer treatment.…”

Section: Wwwchinapharcom Mukhopadhyay S Et Almentioning

confidence: 99%

Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase-mediated cell death

et al. 2014

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Aim: Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. Methods: Cell proliferation, DNA fragmentation, Annexin V binding, immunocytofluorescence, Western blotting, caspase activity assays and luciferase assays were performed to evaluate AGG in human liver cancer cells HepG2. Immunohistochemical staining and TUNEL expression were studied in tumor samples of HepG2-xenografted nude mice.

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Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro

Cited by 89 publications

References 27 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

The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells

Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase-mediated cell death

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