Abstract
Viscum album (VA) preparations consist of aqueous extracts of different types of lectins of VA. Mistletoe lectins have both cytotoxic and immunomodulatory properties that support their study for the development for cancer therapy. However, the mechanisms of the anti- tumoral properties in vivo of mistletoe lectins are not fully understood. Because endothelial cells (EC) play a pivotal role in tumor angiogenesis, we tested the hypothesis that VA extracts induce endothelial cell death and apoptosis. We investigated the effect of various VA preparations on both human venous endothelial cell (HUVEC) and immortalized human venous endothelial cell line (IVEC) using morphologic assessment of EC, FACScan analysis after propidium iodine and annexin V labeling, and detection of cleavage of poly(A)DP-ribose polymerase (PARP). All tested VA preparations, except Iscador P, were cytotoxic in IVEC. Apoptosis, assessed by morphologic examination, annexin V labeling, and Western blot analysis for PARP cleavage, was involved in HUVEC cell death induced by VA preparations derived from plants that grow on oak trees (VA Qu FrF). Results from the present study suggest that VA extract-induced endothelial apoptosis may explain the tumor regression associated with the therapeutic use of VA preparations and support further investigations to develop novel anti-angiogenic compounds based on mistletoe compounds.
Highlights
Viscum album (VA) preparations consist of aqueous extracts from different types of lectins of Viscum album or European mistletoe [1,2]
We demonstrate that VA album preparations, VA Qu FrF, Iscador Qu Spez and, Iscador M Spez, induce death of immortalized endothelial cells (EC) in a dose- and time-dependent manner
Annexin V labeling, and Western blot analysis for poly(A)DP-ribose polymerase (PARP) cleavage, we demonstrate that apoptosis is involved in VA Qu FrF-induced EC death
Summary
Viscum album (VA) preparations consist of aqueous extracts from different types of lectins of Viscum album or European mistletoe [1,2]. In vitro experimental studies have demonstrated both cytotoxic and immunomodulatory properties of ML that may support its anti-tumoral effect [8,9]. Several reported studies on the immunomodulatory effect of mistletoe extracts concern the use of isolated lectins and not the entire preparation used therapeutically, which consist Viscum album (VA) preparations consist of aqueous extracts of different types of lectins of VA. Mistletoe lectins have both cytotoxic and immunomodulatory properties that support their study for the development for cancer therapy. Conclusions: Results from the present study suggest that VA extract-induced endothelial apoptosis may explain the tumor regression associated with the therapeutic use of VA preparations and support further investigations to develop novel anti-angiogenic compounds based on mistletoe compounds
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