A Novel Tetracyclic Peptide, Trapoxin, Induces Phenotypic Change from Transformed to Normal in sis‐Oncogene‐transformed NIH3T3 Cells

A novel tetra cyclic peptide, trapoxin [cyclo(L‐phenylalanyl‐L‐phenylalanyl‐D‐pipecolinyl‐L‐2‐amino‐8‐oxo‐9,10‐epoxy‐decanoyl)], was found to induce the flat phenotype in v‐sis‐transformed NIH3T3 cells at a quite low concentration of 1 ng/ml. Actin stress fiber could be detected after trapoxin treatment. Almost complete reversion into the flat phenotype was observed at 6 h after the administration of the compound. The effect of trapoxin was reversible, when the cell culture was incubated for more than 24 h after its removal. The intracellular level of sis‐mRNA did not decrease with trapoxin treatment at a concentration (50 ng/ml), sufficient to reverse the transformed morphology. Substitution of pipecolinic acid with proline in trapoxin did not change the activity. WF3161, in which leucine was substituted for a phenylalanine of trapoxin, showed only one‐sixteenth of the activity of trapoxin. Reduction of the epoxide residue of trapoxin destroyed the activity.