Synergistic Antitumour Properties ofviscumTTin Alveolar Rhabdomyosarcoma

Abstract

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 withβ-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.ViscumandviscumTTinhibited cell proliferation and induced apoptosis effectively in a dose-dependent manner in vitro and ex vivo, whereasTTshowed only moderate inhibitory effects.viscumTTproved to be more effective than the single extracts and displayed a synergistic effect in vitro and a stronger effect in vivo.viscumTTinduced 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 inviscumTT-induced apoptosis. Additionally,viscumTTchanged the ratio of apoptosis-associated proteins by downregulation of antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance towards apoptosis.viscumTTeffectively reduced tumour volume in patient-derived xenografts in vivo and may be considered a promising substance for rhabdomyosarcoma therapy.