0000000000549197
AUTHOR
B Fleischer
Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95-and TRAIL receptor-mediated apoptosis and chemotherapy
Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy, leading to a poor prognosis of advanced disease. Inhibitors of histone deacetylase (HDACi) induce re-differentiation in tumor cells and thereby re-establish sensitivity towards apoptotic stimuli. HDACi are entering the clinical stage of tumor treatment, and several substances are currently being tested in clinical trials to prove their efficacy in the treatment of leukemias and solid tumors. In this study, we investigated the impact of the HDACi valproic acid (VA) on TRAIL- and CD95-mediated apoptosis in hepatoma cells, as well as its sensitizing effect on a chemotherapeutic agent. Treatment of HepG2 cells with VA increased…
Selective loss of pertussis toxin-sensitive G-proteins from the plasma membrane after antibody-induced internalization of T-cell surface molecules.
Antibody-induced antigenic modulation occurs after binding of antibodies to a variety of cell surface proteins. It is characterized by aggregation and subsequent loss of the molecules from the cell surface, usually by internalization. In this study we have investigated the effect of modulation of the T-cell antigen receptor complex (TCR) and the transferrin receptor (TFR) on the distribution of cholera toxin (CTx)- and pertussis toxin (PTx)-sensitive GTP binding proteins in human T-lymphocytes. Modulation of both the TCR and the TFR induced a selective shift of PTx-sensitive G-proteins from the plasma membrane to a high density membrane fraction enriched for lysosomal membranes. The distrib…