Title of article :
Synthesis and cellular characterization of the detransformation agent, (−)-depudecin Original Research Article
Author/Authors :
Junichi Shimada، نويسنده , , Ho Jeong Kwon، نويسنده , , Masaya Sawamura، نويسنده , , Stuart L. Schreiber، نويسنده ,
Issue Information :
ماهنامه با شماره پیاپی سال 1995
Abstract :
Background: (−)-Depudecin is a fungal metabolite that reverts the rounded phenotype of NIH3T3 fibroblasts transformed with v-ras and v-src oncogenes to the flat phenotype of the nontransformed parental cells. The mechanism of action of this detransformation agent is unknown. Although depudecin appears to be an excellent molecule for probing signaling pathways that regulate changes in the cytoskeletal architecture, reagents based on depudecin are not available as it has not yet been successfully synthesized. We therefore set out to synthesize (−)-depudecin.
Results: An asymmetric synthesis of (−)-depudecin has been developed. A cell staining assay has been used to reveal the ability of synthetic depudecin, but not several structural variants, to induce a flattened morphology in v-Ha-ras-transformed NlH3T3 cells.This assay also shows that depudecin induces an intricate network of actin stress fibers in these cells and in MG63 osteosarcoma cells and reveals the essential role of the epoxide and hydroxyl moieties in depudecin. Cycloheximide and actinomycin D inhibited the ability of depudecin to induce a morphological change, suggesting that both mRNA synthesis and de novo protein synthesis are required for depudecin-mediated suppression of the transformed phenotypes in ras-transformed cells.
Keywords :
* detransformation , * signal transduction , * depudecin , * total synthesis , * actin stress fibers
Journal title :
Chemistry and Biology
Journal title :
Chemistry and Biology