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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

In vivo efficacy of Viscum album L. extracts.NOD/SCID/IL2rg mice carrying systemic human promyelotic leukaemia cells (HL-60) were treated with a dose-escalation regimen of 20/40/60/ mg/kg oleanolic acid (TT), 0.3/0.4/0.5 μg/kg lectin (viscum) or a combination thereof (viscumTT), three times per week for two weeks post-transplantation of cells. Each concentration were given twice (i.v.), starting on day three after tumor cell injection. One group was treated with cytarabine and one with cytarabine plus viscumTT. Control mice received equal amounts of cyclodextrins. The treatment with viscumTT had a significant therapeutic advantage compared to the single extracts TT and viscum.
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pone.0133892.g006: In vivo efficacy of Viscum album L. extracts.NOD/SCID/IL2rg mice carrying systemic human promyelotic leukaemia cells (HL-60) were treated with a dose-escalation regimen of 20/40/60/ mg/kg oleanolic acid (TT), 0.3/0.4/0.5 μg/kg lectin (viscum) or a combination thereof (viscumTT), three times per week for two weeks post-transplantation of cells. Each concentration were given twice (i.v.), starting on day three after tumor cell injection. One group was treated with cytarabine and one with cytarabine plus viscumTT. Control mice received equal amounts of cyclodextrins. The treatment with viscumTT had a significant therapeutic advantage compared to the single extracts TT and viscum.

Mentions: The S1 Dataset represents the data underlying the results of Figs 1–6. These data are the basis of all presenting diagrams within this publication.


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)

In vivo efficacy of Viscum album L. extracts.NOD/SCID/IL2rg mice carrying systemic human promyelotic leukaemia cells (HL-60) were treated with a dose-escalation regimen of 20/40/60/ mg/kg oleanolic acid (TT), 0.3/0.4/0.5 μg/kg lectin (viscum) or a combination thereof (viscumTT), three times per week for two weeks post-transplantation of cells. Each concentration were given twice (i.v.), starting on day three after tumor cell injection. One group was treated with cytarabine and one with cytarabine plus viscumTT. Control mice received equal amounts of cyclodextrins. The treatment with viscumTT had a significant therapeutic advantage compared to the single extracts TT and viscum.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133892.g006: In vivo efficacy of Viscum album L. extracts.NOD/SCID/IL2rg mice carrying systemic human promyelotic leukaemia cells (HL-60) were treated with a dose-escalation regimen of 20/40/60/ mg/kg oleanolic acid (TT), 0.3/0.4/0.5 μg/kg lectin (viscum) or a combination thereof (viscumTT), three times per week for two weeks post-transplantation of cells. Each concentration were given twice (i.v.), starting on day three after tumor cell injection. One group was treated with cytarabine and one with cytarabine plus viscumTT. Control mice received equal amounts of cyclodextrins. The treatment with viscumTT had a significant therapeutic advantage compared to the single extracts TT and viscum.
Mentions: The S1 Dataset represents the data underlying the results of Figs 1–6. These data are the basis of all presenting diagrams within this publication.

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