A novel tetracyclic peptide, trapoxin, induces phenotypic change from transformed to normal in sis-oncogene-transformed NIH3T3 cells.
A novel tetracyclic 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.
Yoshida
H
H
Department of Microbiology, Shionogi Research Laboratories, Shionogi & Co., Osaka.
Sugita
K
K
D016475:3T3 Cells; D000199:Actins / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D007700:Kinetics; D051379:Mice; D020575:Oncogene Proteins v-sis; D009857:Oncogenes; D010455:Peptides; D010456:Peptides, Cyclic / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*
D000199:Actins; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D020575:Oncogene Proteins v-sis; D010455:Peptides; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; C067070:trapoxin A