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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.

Delebinski CI, Twardziok M, Kleinsimon S, Hoff F, Mulsow K, Rolff J, Jäger S, Eggert A, Seifert G - PLoS ONE (2015)

Bottom Line: Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Oncology/Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité -Universitaetsmedizin, Berlin, Germany.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Mistletoe extracts induce apoptosis in acute myeloid leukaemia cells ex vivo.Mononuclear cells obtained from bone marrow aspirates of two patients with acute myeloid leukaemia (patient 1 (m; 17 years); patient 2 (m, 10 years)) were incubated with the depicted VAEs for 18 h. Induction of apoptosis (n = 2), mitochondrial transmembrane potential (n = 1) and activation of caspase-8 / -9 (n = 1) were measured by flow cytometry. VAEs induce apoptosis with involvement of mitochondria and activation of caspases in AML patients ex vivo, viscumTT shows synergistic apoptosis induction.
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pone.0133892.g005: Mistletoe extracts induce apoptosis in acute myeloid leukaemia cells ex vivo.Mononuclear cells obtained from bone marrow aspirates of two patients with acute myeloid leukaemia (patient 1 (m; 17 years); patient 2 (m, 10 years)) were incubated with the depicted VAEs for 18 h. Induction of apoptosis (n = 2), mitochondrial transmembrane potential (n = 1) and activation of caspase-8 / -9 (n = 1) were measured by flow cytometry. VAEs induce apoptosis with involvement of mitochondria and activation of caspases in AML patients ex vivo, viscumTT shows synergistic apoptosis induction.

Mentions: To investigate whether VAE treatment was able to induce apoptosis in primary tumour cells (ex vivo), bone marrow aspirates of two patients with childhood AML were treated with increasing concentrations of viscum, TT and viscumTT. As shown in Fig 5, VAE treatment induced apoptosis accompanied by the loss of mitochondrial transmembrane potential in both ex vivo samples in a concentration-dependent manner. Moreover, we were able to confirm the synergistic effect of viscumTT ex vivo (*Fp>1). In addition, the measurement of active caspase-8 and -9 verified our in vitro data after VAE treatment.


A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo.

Delebinski CI, Twardziok M, Kleinsimon S, Hoff F, Mulsow K, Rolff J, Jäger S, Eggert A, Seifert G - PLoS ONE (2015)

Mistletoe extracts induce apoptosis in acute myeloid leukaemia cells ex vivo.Mononuclear cells obtained from bone marrow aspirates of two patients with acute myeloid leukaemia (patient 1 (m; 17 years); patient 2 (m, 10 years)) were incubated with the depicted VAEs for 18 h. Induction of apoptosis (n = 2), mitochondrial transmembrane potential (n = 1) and activation of caspase-8 / -9 (n = 1) were measured by flow cytometry. VAEs induce apoptosis with involvement of mitochondria and activation of caspases in AML patients ex vivo, viscumTT shows synergistic apoptosis induction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526680&req=5

pone.0133892.g005: Mistletoe extracts induce apoptosis in acute myeloid leukaemia cells ex vivo.Mononuclear cells obtained from bone marrow aspirates of two patients with acute myeloid leukaemia (patient 1 (m; 17 years); patient 2 (m, 10 years)) were incubated with the depicted VAEs for 18 h. Induction of apoptosis (n = 2), mitochondrial transmembrane potential (n = 1) and activation of caspase-8 / -9 (n = 1) were measured by flow cytometry. VAEs induce apoptosis with involvement of mitochondria and activation of caspases in AML patients ex vivo, viscumTT shows synergistic apoptosis induction.
Mentions: To investigate whether VAE treatment was able to induce apoptosis in primary tumour cells (ex vivo), bone marrow aspirates of two patients with childhood AML were treated with increasing concentrations of viscum, TT and viscumTT. As shown in Fig 5, VAE treatment induced apoptosis accompanied by the loss of mitochondrial transmembrane potential in both ex vivo samples in a concentration-dependent manner. Moreover, we were able to confirm the synergistic effect of viscumTT ex vivo (*Fp>1). In addition, the measurement of active caspase-8 and -9 verified our in vitro data after VAE treatment.

Bottom Line: Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Oncology/Haematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité -Universitaetsmedizin, Berlin, Germany.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus