ZSTK474 is a new PI3K inhibitor with strong antitumor activity against human cancer xenografts without toxic effects in critical organs. ZSTK474 merits further investigation as an anticancer drug.
Somatic embryogenesis of the carrot (Daucus carota L.) depends on a set of factors, some of which accumulate in culture medium (conditioned medium, CM). When embryogenic cell clusters were transferred to an embryo-inducing medium, addition of CM derived from somatic embryo culture markedly stimulated somatic embryo formation. The active principles were purified using a simple bioassay system and identified to be phytosulfokines (PSKs), sulfated oligopeptide growth factors originally isolated from a CM derived from asparagus (Asparagus officinalis L.) mesophyll culture. Quantification studies using a competition ELISA system employing an anti-PSK-alpha polyclonal antibody showed that PSK production might be related to growth of cells, rather than development of somatic embryos. Thus the stimulatory effect of PSK on somatic embryo formation might be due to promotion of cell proliferation.
We evaluated free radical scavenging activity of the water, methanol and chloroform extracts of propolis in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and xanthine-xanthine oxidase (XOD) generated superoxide anion assay systems. The free radical scavenging activity guided fractionation and chemical analysis led to the isolation of a new compound, propol {3-[4-hydroxy-3-(3-oxo-but-1-enyl)-phenyl]-acrylic acid) from the water extract, which was more potent than most common antioxidants such as vitamin C and vitamin E (α-tocopherol) in these assay systems.
Clostridium perfringens alpha-toxin induces the generation of superoxide anion (O2
−) via production of 1,2-diacylglycerol (DG) in rabbit neutrophils. The mechanism of the generation, however, remains poorly understood. Here we report a novel mechanism for the toxin-induced production of O2
− in rabbit neutrophils. Treatment of the cells with the toxin resulted in tyrosine phosphorylation of a protein of about 140 kDa. The protein reacted with anti-TrkA (nerve growth factor high-affinity receptor) antibody and bound nerve growth factor. Anti-TrkA antibody inhibited the production of O2
− and binding of the toxin to the protein. The toxin induced phosphorylation of 3-phosphoinositide-dependent protein kinase 1 (PDK1). K252a, an inhibitor of TrkA receptor, and LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), reduced the toxin-induced production of O2
− and phosphorylation of PDK1, but not the formation of DG. These inhibitors inhibited the toxin-induced phosphorylation of protein kinase C θ (PKCθ). U73122, a phospholipase C (PLC) inhibitor, and pertussis toxin inhibited the toxin-induced generation of O2
− and formation of DG, but not the phosphorylation of PDK1. These observations show that the toxin independently induces production of DG through activation of endogenous PLC and phosphorylation of PDK1 via the TrkA receptor signaling pathway and that these events synergistically activate PKCθ in stimulating an increase in O2
−. In addition, we show the participation of mitogen-activated protein kinase-associated signaling events via activation of PKCθ in the toxin-induced generation of O2
−.
The methanol extract of Brazilian propolis was fractionated by HPLC, based on HuH13 (human hepatocellular carcinoma) cell cytotoxicity assay. Two isomers of diterpenoid with a molecular formula of C20H30O3 (MW: 318.46) were isolated. The structures of these colorless compounds were determined as clerodane diterpenoids (I, 15-oxo-3, 13Z-kolavadien-17-oic acid; II, 15-oxo-3Z, 13E-kolavadien-n-oic acid)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.