Selective killing of human T cell lymphotropic virus type I-transformed cell lines by a damavaricin Fc derivative.
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.
Ito
S
S
Shin-Etsu Chemical Co., Ltd., Tokyo.
Yamamoto
N
N
Nomoto
K
K
Sasaki
K
K
Onodera
K
K
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004247:DNA / Q000096:biosynthesis; D004229:Dithiothreitol / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology; D008623:Mercaptoethanol / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology; D013310:Streptovaricin / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D013310:Streptovaricin; D008623:Mercaptoethanol; D010672:Phenytoin; C059809:damavaricin Fc pentyl ether; D004247:DNA; D011802:Quinidine; D011188:Potassium; D002118:Calcium; D004229:Dithiothreitol