Induction of apoptosis of endothelial cells by Viscum album: a role for anti-tumoral properties of mistletoe lectins.
BACKGROUND
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.


METHODS
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).


RESULTS
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).


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.
Duong Van Huyen
Jean-Paul
JP
INSERM U430, Hôpital Broussais, Paris, France.
Bayry
Jagadeesh
J
Delignat
Sandrine
S
Gaston
Anh Thu
AT
Michel
Odile
O
Bruneval
Patrick
P
Kazatchkine
Michel D
MD
Nicoletti
Antonino
A
Kaveri
Srini V
SV
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D037121:Plant Lectins / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D028182:Viscum album / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D037121:Plant Lectins