streptovaricin-c and Leukemia--T-Cell

n-Pentyl ether of damavaricin Fc (n-pentyl DvFc) preferentially killed human T-cell lymphotropic virus type I (HTLV-I)-transformed cell lines. The mechanism of action of the drug was investigated using MT-4 cells. Cytotoxic action was diminished by the removal of n-pentyl DvFc from the culture or by the addition of sulfhydryl compounds such as 2-mercaptoethanol and dithiothreitol. The killing activity of n-pentyl DvFc was also diminished by membrane-acting agents including quinidine and diphenylhydantoin. Influx and subsequent efflux of Ca2+ were observed when either HTLV-I infected (MT-4 cells) or uninfected cells were treated with n-pentyl DvFc. An efflux of K+ was observed in HTLV-I infected MT-4 cells immediately after the exposure of the cells to n-pentyl DvFc. The K+ efflux, however, was not observed in the uninfected T cells. n-Pentyl DvFc seems to act primarily on the cell surface of MT-4 cells, leading to the perturbation of membrane function. The restoration of cell growth, however, is critically dependent on the presence of dithiothreitol and 2-mercaptoethanol, implying a role for a free sulfhydryl group in the killing activity.

Topics: Anti-Bacterial Agents; Antiviral Agents; Calcium; Cell Line, Transformed; Cell Membrane; Cell Membrane Permeability; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Dithiothreitol; DNA; Human T-lymphotropic virus 1; Humans; Leukemia, T-Cell; Mercaptoethanol; Phenytoin; Potassium; Quinidine; Streptovaricin; T-Lymphocytes