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Monika Twardziok - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic and proteomic insight into the effects of a defined european mistletoe extract in ewing sarcoma cells reveals cellular stress responses
BMC Complementary and Alternative Medicine, 2017Co-Authors: Angelika Eggert, Monika Twardziok, Sebastian Jager, David Meierhofer, Stefan T Borno, Bernd Timmermann, Sengul Boral, Catharina I. DelebinskiAbstract:The hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (Viscum album L.). Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo. We recreated a total mistletoe effect (ViscumTT) by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilised with cyclodextrins and analysed the effects of ViscumTT and the single extracts on TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling. Treatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism of action of Viscum, TT and ViscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded protein response. While Viscum and ViscumTT extract treatment indicate response to oxidative stress and activation of stress-mediated MAPK signalling, TT extract treatment suggests the involvement of TLR signalling and autophagy. Since the combinatory extract ViscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.
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multiple active compounds from Viscum album l synergistically converge to promote apoptosis in ewing sarcoma
PLOS ONE, 2016Co-Authors: Angelika Eggert, Georg Seifert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Catharina I. DelebinskiAbstract:Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with Viscum, TT and ViscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with Viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while ViscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that ViscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.
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a natural combination extract of Viscum album l containing both triterpene acids and lectins is highly effective against aml in vivo
PLOS ONE, 2015Co-Authors: Catharina I. Delebinski, Angelika Eggert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Florian Hoff, Katharina Mulsow, Georg SeifertAbstract:Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (Viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of Viscum and TT extracts (ViscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of ViscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination ViscumTT may have a potential therapeutic value for the treatment AML.
Gunver S. Kienle - One of the best experts on this subject based on the ideXlab platform.
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long term tumor free survival in a metastatic pancreatic carcinoma patient with folfirinox mitomycin high dose fever inducing Viscum album extracts and subsequent r0 resection a case report
Medicine, 2018Co-Authors: Paul G Werthmann, Pia Inter, Thilo Welsch, Annekathrin Sturm, Robert Grutzmann, Markus Debus, Martingunther Sterner, Gunver S. KienleAbstract:AbstractRationale:Metastatic pancreatic cancer has a dismal prognosis. Many patients seek integrative care as an add-on to their conventional cancer treatment. Viscum album extracts (VAE)—widely used as an adjunct to cancer treatment—have cytotoxic, apoptogenic, and immune stimulatory properties. A
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complete remission and long term survival of a patient with melanoma metastases treated with high dose fever inducing Viscum album extract a case report
Medicine, 2017Co-Authors: Paul G Werthmann, Alexander Hintze, Gunver S. KienleAbstract:AbstractIntroduction:Metastatic malignant cutaneous melanoma (MCM)—a highly immunogenic cancer—typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects.Case presentation:A 66-year-old MCM patient with newly diagnosed lymph node m
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Disappearance of an advanced adenomatous colon polyp after intratumoural injection with Viscum album (European mistletoe) extract: a case report.
Journal of gastrointestinal and liver diseases : JGLD, 2014Co-Authors: Tido Von Schoen-angerer, Helmut Kiene, Jan Vagedes, Andreas Goyert, Harald Merckens, Gunver S. KienleAbstract:Background & Aim: Extracts of Viscum album (European mistletoe) have immune-stimulatory and cytotoxic eects, with trials showing a well-established eect on the quality of life and prolonged survival in patients with advanced pancreatic cancer. Regression of tumours following intratumoural injection with Viscum album extract has been documented in individual cases. However, its inuence on colon polyps has not been investigated. Case presentation: We present the case of a 78-year-old Caucasian male who had undergone hemi-colectomy for a stage IIIC colon cancer but who refused adjuvant chemotherapy. Five years later a newly detected high- grade dysplasia colon adenoma was discovered; however, the adenoma could not be resected endoscopically and the patient did not consent to surgery. Intratumoural injections with Viscum album L extract (Quercus; Iscador®Qu) were administered twice in an attempt to limit tumour growth. Eight months aer the second intratumoural injection the adenoma had disappeared and biopsy revealed no intraepithelial dysplasia or adenoma. Conclusions: �is is therst report showing complete regression of a colon adenoma aer intratumoural injection with Viscum album extract. Prospective studies should evaluate if the treatment eect is reproducible and if this approach could be a useful pre-operative measure for colon adenomas too large for endoscopic resection.
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safety of higher dosages of Viscum album l in animals and humans systematic review of immune changes and safety parameters
BMC Complementary and Alternative Medicine, 2011Co-Authors: Gunver S. Kienle, Renate Grugel, Helmut KieneAbstract:Background Viscum album L extracts (VAE, mistletoe) and isolated mistletoe lectins (ML) have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects.
Catharina I. Delebinski - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic and proteomic insight into the effects of a defined european mistletoe extract in ewing sarcoma cells reveals cellular stress responses
BMC Complementary and Alternative Medicine, 2017Co-Authors: Angelika Eggert, Monika Twardziok, Sebastian Jager, David Meierhofer, Stefan T Borno, Bernd Timmermann, Sengul Boral, Catharina I. DelebinskiAbstract:The hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (Viscum album L.). Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo. We recreated a total mistletoe effect (ViscumTT) by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilised with cyclodextrins and analysed the effects of ViscumTT and the single extracts on TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling. Treatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism of action of Viscum, TT and ViscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded protein response. While Viscum and ViscumTT extract treatment indicate response to oxidative stress and activation of stress-mediated MAPK signalling, TT extract treatment suggests the involvement of TLR signalling and autophagy. Since the combinatory extract ViscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.
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multiple active compounds from Viscum album l synergistically converge to promote apoptosis in ewing sarcoma
PLOS ONE, 2016Co-Authors: Angelika Eggert, Georg Seifert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Catharina I. DelebinskiAbstract:Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with Viscum, TT and ViscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with Viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while ViscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that ViscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.
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impact of mistletoe triterpene acids on the uptake of mistletoe lectin by cultured tumor cells
PLOS ONE, 2016Co-Authors: Katharina Mulsow, Catharina I. Delebinski, Georg Seifert, Thomas Enzlein, Sebastian Jaeger, Matthias F MelzigAbstract:Complementary treatment possibilities for the therapy of cancer are increasing in demand due to the severe side effects of the standard cytostatics used in the first-line therapy. A common approach as a complementary treatment is the use of aqueous extracts of Viscum album L. (Santalaceace). The therapeutic activity of these extracts is attributed to Mistletoe lectins which are Ribosome-inactivating proteins type II. Besides these main constituents the extract of Viscum album L. comprises also a mixture of lipophilic ingredients like triterpene acids of the oleanane, lupane and ursane type. However, these constituents are not contained in commercially available aqueous extracts due to their high lipophilicity and insolubility in aqueous extraction media. To understand the impact of the extract ingredients in cancer therapy, the intracellular uptake of the mistletoe lectin I (ML) by cultured tumor cells was investigated in relation to the mistletoe triterpene acids, mainly oleanolic acid. Firstly, these hydrophobic triterpene acids were solubilized using cyclodextrins (“TT” extract). Afterwards, the uptake of either single compounds (isolated ML and the aqueous “Viscum” extract) or in combination with the TT extract (ML+TT, ViscumTT), was analyzed. The uptake of ML was studied inTHP-1-, HL-60-, 143B- and Ewing TC-71-cells and determined after 30, 60 and 120 minutes by an enzyme linked immunosorbent assay which quantifies the A-chain of the hololectin. It could be shown that the intracellular uptake after 120 minutes amounted to 20% in all cell lines after incubation with ViscumTT. The studies further revealed that the uptake in THP-1-, HL-60- and Ewing TC-71-cells was independent of the addition of TT extract. Interestingly, the uptake of ML by 143B-cells could only be measured after addition of triterpenes pointing to resistance to mistletoe lectin.
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a natural combination extract of Viscum album l containing both triterpene acids and lectins is highly effective against aml in vivo
PLOS ONE, 2015Co-Authors: Catharina I. Delebinski, Angelika Eggert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Florian Hoff, Katharina Mulsow, Georg SeifertAbstract:Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (Viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of Viscum and TT extracts (ViscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of ViscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination ViscumTT may have a potential therapeutic value for the treatment AML.
Sebastian Jager - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic and proteomic insight into the effects of a defined european mistletoe extract in ewing sarcoma cells reveals cellular stress responses
BMC Complementary and Alternative Medicine, 2017Co-Authors: Angelika Eggert, Monika Twardziok, Sebastian Jager, David Meierhofer, Stefan T Borno, Bernd Timmermann, Sengul Boral, Catharina I. DelebinskiAbstract:The hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (Viscum album L.). Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo. We recreated a total mistletoe effect (ViscumTT) by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilised with cyclodextrins and analysed the effects of ViscumTT and the single extracts on TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling. Treatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism of action of Viscum, TT and ViscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded protein response. While Viscum and ViscumTT extract treatment indicate response to oxidative stress and activation of stress-mediated MAPK signalling, TT extract treatment suggests the involvement of TLR signalling and autophagy. Since the combinatory extract ViscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.
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multiple active compounds from Viscum album l synergistically converge to promote apoptosis in ewing sarcoma
PLOS ONE, 2016Co-Authors: Angelika Eggert, Georg Seifert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Catharina I. DelebinskiAbstract:Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with Viscum, TT and ViscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with Viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while ViscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that ViscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.
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a natural combination extract of Viscum album l containing both triterpene acids and lectins is highly effective against aml in vivo
PLOS ONE, 2015Co-Authors: Catharina I. Delebinski, Angelika Eggert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Florian Hoff, Katharina Mulsow, Georg SeifertAbstract:Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (Viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of Viscum and TT extracts (ViscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of ViscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination ViscumTT may have a potential therapeutic value for the treatment AML.
Angelika Eggert - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic and proteomic insight into the effects of a defined european mistletoe extract in ewing sarcoma cells reveals cellular stress responses
BMC Complementary and Alternative Medicine, 2017Co-Authors: Angelika Eggert, Monika Twardziok, Sebastian Jager, David Meierhofer, Stefan T Borno, Bernd Timmermann, Sengul Boral, Catharina I. DelebinskiAbstract:The hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (Viscum album L.). Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo. We recreated a total mistletoe effect (ViscumTT) by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilised with cyclodextrins and analysed the effects of ViscumTT and the single extracts on TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling. Treatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism of action of Viscum, TT and ViscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded protein response. While Viscum and ViscumTT extract treatment indicate response to oxidative stress and activation of stress-mediated MAPK signalling, TT extract treatment suggests the involvement of TLR signalling and autophagy. Since the combinatory extract ViscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.
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multiple active compounds from Viscum album l synergistically converge to promote apoptosis in ewing sarcoma
PLOS ONE, 2016Co-Authors: Angelika Eggert, Georg Seifert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Catharina I. DelebinskiAbstract:Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (Viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with Viscum, TT and ViscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with Viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while ViscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that ViscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.
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a natural combination extract of Viscum album l containing both triterpene acids and lectins is highly effective against aml in vivo
PLOS ONE, 2015Co-Authors: Catharina I. Delebinski, Angelika Eggert, Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jager, Florian Hoff, Katharina Mulsow, Georg SeifertAbstract:Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (Viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of Viscum and TT extracts (ViscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of ViscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination ViscumTT may have a potential therapeutic value for the treatment AML.
