A MULTISAMPLE ASSAY FOR INHIBITORS OF PHOSPHATIDYLINOSITOL PHOSPHOLIPASE-C - IDENTIFICATION OF NATURALLY-OCCURRING PEPTIDE INHIBITORS WITH ANTIPROLIFERATIVE ACTIVITY

A convenient and reliable multisample assay for the screening of inhib itors of the growth factor signalling enzyme phosphatidylinositol spec ific phospholipase C (PtdInsPLC) has been developed. Three naturally o ccurring peptide inhibitors of PtdInsPLC have been identified, myrorid in K, streptothricin B and edeine, with IC50 values of 8.3, 6.7 and 16 .1 mu M, respectively. All three peptides inhibited colony formation o f HT-29 human colon adenocarcinoma cells, with IC50 values of 7.2, 3.9 and 13.0 mu M, 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 cel l growth inhibition and antitumour properties of the peptide compounds .