Interruption of TPA-induced signals by an antiviral and antitumoral xanthate compound: inhibition of a phospholipase C-type reaction.
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.
Müller-Decker
K
K
Institute for Virus Research, German Cancer Research Center, Heidelberg, FRG.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004075:Diglycerides / Q000096:biosynthesis; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D009636:Norbornanes; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010743:Phospholipids / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001952:Bridged-Ring Compounds; D004075:Diglycerides; D009636:Norbornanes; D010713:Phosphatidylcholines; D010743:Phospholipids; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate