Aqueous mistletoe extracts from the European mistletoe (Viscum album) contain
mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic
triterpene acids, which do not occur in conventional mistletoe preparations,
were solubilised with β-cyclodextrins. The combination of an aqueous extract
(viscum) and a triterpene-containing extract (TT) recreated a whole mistletoe
extract (viscumTT). These extracts were tested on rhabdomyosarcoma in vitro,
ex vivo, and in vivo with regard to anticancer effects. Viscum and viscumTT
inhibited cell proliferation and induced apoptosis effectively in a dose-
dependent manner in vitro and ex vivo, whereas TT showed only moderate
inhibitory effects. viscumTT proved to be more effective than the single
extracts and displayed a synergistic effect in vitro and a stronger effect in
vivo. viscumTT induced apoptosis via the extrinsic and intrinsic pathways,
evidenced by the loss of mitochondrial membrane potential and activation of
CASP8 and CASP9. CASP10 inhibitor inhibited apoptosis effectively, emphasising
the importance of CASP10 in viscumTT-induced apoptosis. Additionally, viscumTT
changed the ratio of apoptosis-associated proteins by downregulation of
antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance
towards apoptosis. viscumTT effectively reduced tumour volume in patient-
derived xenografts in vivo and may be considered a promising substance for
rhabdomyosarcoma therapy
