Anti-FYN monoclonal antibody, clone 3B21

Fyn-related kinase (FRK), a member of the Src-related tyrosine kinase family, functions as a tumor suppressor in several malignancies. We previously showed that FRK overexpression inhibited the growth of glioma cells. However, it is unknown whether FRK is equally effective against intracranial glioma in vivo, and the mechanism by which FRK influences glioma cell growth remains unclear. In this study, we found that tumor volume was reduced by about one-third in mice with FRK overexpression, which showed improved survival relative to controls. Immunofluorescence analysis revealed that FRK overexpression inhibited glioma cell proliferation and induced their apoptosis. Importantly, in vitro we further found that FRK decreased the expression of integrin subunit beta 1 (ITGB1) at both the mRNA and protein levels. FRK also inhibited transactivation by ITGB1, resulting in the suppression of its target proteins AKT and focal adhesion kinase (FAK). ITGB1 overexpression promoted glioma cell growth and partially reduced FRK-induced growth suppression. These results indicate that FRK inhibits human glioma growth via regulating ITGB1/FAK signaling and provide a potential therapeutic target for the treatment of glioma. (C) 2019 Published by Elsevier Inc.

Hyperoside, isolated fromDrosera rotundifoliaL., seeds ofCuscuta chinensisLam., orHypericum perforatumL., originally showed to possess an antifungal and antibacterial activity, while recently showed the protective effects against oxidative stress-induced liver injury. This study investigated such a protective effect of hyperoside and the underlying molecular mechanismsin vitroand in carbon tetrachloride (CCl4)-injured rat livers. The data showed that hyperoside was able to prevent the oxidative stress-induced liver morphological changes and CCl4-induced rat liver injury. Hyperoside reversed the decrease of superoxidase dismutase (SOD) level and the increase of malondialdehyde (MDA) levelin vivo. Moreover, hyperoside regulated the pleckstrin homology (PH) domain leucine-rich repeat protein phosphatase 2 (PHLPP2)-protein kinase B (AKT)-glycogen synthase kinase 3 beta (GSK-3 beta) signaling pathway in tert-butylhydroquinone (t-BHP)-treated liver cells, e.g., Hyperoside reduced PHLPP2 expression to activate AKT phosphorylation, induce GSK-3 beta phosphorylation, and then increased nuclear factor erythroid-2-related factor 2 (Nrf2) nuclear translocation, reduced nuclear translocation of phosphorylated Fyn, and promoted heme oxygenase-1 (HO-1) expressionin vivoandin vitro. In contrast, siRNA-mediated knockdown of PHLPP2 expression enhanced hyperoside-mediated activation of the AKT-GSK-3 beta kinase pathway in liver cells. In conclusion, the present study demonstrated that hyperoside could protect against oxidative stress-induced liver injury by regulating the PHLPP2-AKT-GSK-3 beta signaling pathwayin vivoandin vitro.