Interruption of TPA-induced signals by an antiviral and antitumoral xanthate compound: inhibition of a phospholipase C-type reaction

Biochem Biophys Res Commun. 1989 Jul 14;162(1):198-205. doi: 10.1016/0006-291x(89)91981-5.

Abstract

The effect of tricyclodecan-9-yl-xanthogenate on the phorbolester TPA induced changes in phosphatidylcholine metabolism was investigated. In the simultaneous presence of the xanthate TPA failed to stimulate the metabolic [32P] turnover of the major phospholipids. The precursor molecule [3H] choline was incorporated into phosphatidylcholine after pulse labeling in TPA/D609-treated cells. Thus, the reduction of the [32P] phosphatidylcholine turnover did not appear to result from an inhibition of the TPA-stimulated phosphatidylcholine biosynthesis. However, the xanthate exerted an inhibitory effect on the TPA-stimulated liberation of [3H] phosphorylcholine from [3H] phosphatidylcholine in cells prelabeled with [3H] choline. Furthermore, the TPA-induced rise in the diacylglycerol level was reduced in the presence of the compound. Thus, these results provide evidence that the xanthate inhibits a TPA-induced phospholipase C activity in the intact cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / pharmacology*
  • Bridged-Ring Compounds / pharmacology*
  • Cell Line
  • Cricetinae
  • Diglycerides / biosynthesis
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism
  • Humans
  • Norbornanes
  • Phosphatidylcholines / biosynthesis
  • Phospholipids / metabolism
  • Signal Transduction / drug effects*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Thiocarbamates
  • Thiones / pharmacology*
  • Tumor Cells, Cultured / enzymology
  • Tumor Cells, Cultured / metabolism
  • Type C Phospholipases / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Bridged-Ring Compounds
  • Diglycerides
  • Norbornanes
  • Phosphatidylcholines
  • Phospholipids
  • Thiocarbamates
  • Thiones
  • tricyclodecane-9-yl-xanthogenate
  • Type C Phospholipases
  • Tetradecanoylphorbol Acetate