Anti-Human CASP9 (Phospho-Ser144) polyclonal antibody

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 beta-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.

Exposure to ZnO nanoparticles (NPs) might modulate endoplasmic reticulum (ER) stress-autophagy gene expression, but the possible influence of hydrophobic surface coating on these responses was less studied. This study used A549-macrophage co-culture as the in vitro model for lung barrier and investigated the toxicity of pristine and hydrophobic ZnO NPs. Pristine and hydrophobic NPs exhibited different Zeta potential and solubility in water, which suggested that hydrophobic surface coating might alter the colloidal aspects of ZnO NPs. However, pristine and hydrophobic ZnO NPs induced cytotoxicity and reduced the release of soluble monocyte chemotactic protein-1 (sMCP-1) in A549-macrophage co-culture to a similar extent. Exposure to pristine ZnO NPs significantly promoted the expression of ER stress-apoptosis genes, namely DDIT3, XBP-ls, CASP9, CASP12 and BAX (p < 0.05), but hydrophobic ZnO NPs only significantly promoted the expression of BAX (p < 0.05). Exposure to pristine ZnO NPs also significantly reduced the expression of autophagic gene BECN1 (p < 0.05) but not ATG7 (p > 0.05), whereas hydrophobic ZnO NPs significantly reduced the expression of ATG7 and BECN1 (p < 0.01). Moreover, the expression of XBP-ls, HSPA5, CASP9, CASP12, BAX and ATG7 in pristine ZnO NP-exposed co-culture was significantly lower than that in hydrophobic ZnO NP-exposed co-culture (p < 0.05). In conclusion, hydrophobic surface coating might influence the colloidal aspects of ZnO NPs and alter ER stress-apoptosis-autophagy gene expression pattern by pristine ZnO NPs in A549-macrophage co-culture.