title: A multisample assay for inhibitors of phosphatidylinositol phospholipase C: identification of naturally occurring peptide inhibitors with antiproliferative activity.
abstract: A convenient and reliable multisample assay for the screening of inhibitors of the growth factor signalling enzyme phosphatidylinositol specific phospholipase C (PtdInsPLC) has been developed. Three naturally occurring peptide inhibitors of PtdInsPLC have been identified, myroridin K, streptothricin B and edeine, with IC50 values of 8.3, 6.7 and 16.1 microM, respectively. All three peptides inhibited colony formation of HT-29 human colon adenocarcinoma cells, with IC50 values of 7.2, 3.9 and 13.0 microM, respectively. The compounds also inhibited the growth of other human cancer cells in culture. One of the peptides, myroridin K, has previously been reported to have in vivo antitumour activity. It is possible that inhibition of PtdInsPLC is responsible for the cell growth inhibition and antitumour properties of the peptide compounds.
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson 85724.
authors.forename: S R
authors.initials: SR
authors.lastname: Hill
authors.forename: R
authors.initials: R
authors.lastname: Bonjouklian
authors.forename: G
authors.initials: G
authors.lastname: Powis
authors.forename: R T
authors.initials: RT
authors.lastname: Abraham
authors.forename: C L
authors.initials: CL
authors.lastname: Ashendel
authors.forename: L H
authors.initials: LH
authors.lastname: Zalkow
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004486:Edeine / Q000494:pharmacology; D006801:Humans; D010455:Peptides; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D013309:Streptothricins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D004486:Edeine; D013309:Streptothricins; C026530:myroridin K; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase