Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression

Oncogene. 1997 Nov 20;15(21):2625-31. doi: 10.1038/sj.onc.1201443.


Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cell lines and to revert their cell morphology to be flat. In the radicicol-treated flat cells, actin stress fiber bundles were reorganized. Since this effect of radicicol on these cell lines was inhibited by cycloheximide, de novo protein synthesis is required for the morphological reversion. Screening of cellular proteins enhanced in response to radicicol by two-dimensional gel electrophoresis suggested that the amount of gelsolin, an actin regulatory protein, was distinctly increased upon radicicol treatment. Western blot and Northern blot analyses showed that radicicol enhanced transcription of the gelsolin gene in human carcinoma cell lines, as a result of which the amount of gelsolin was increased several folds. Injection with an anti-gelsolin antibody into cells and successive treatment with radicicol resulted in approximately 80% reduction of the number of flat cells with stress fibers in comparison with controls treated with an irrelevant antibody. These results show that elevated expression of gelsolin is associated, at least in part, with the suppression of transformation and the restoration of actin stress fibers in human carcinoma cells by radicicol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Actin Cytoskeleton / drug effects
  • Animals
  • Cell Transformation, Neoplastic / drug effects*
  • Cycloheximide / pharmacology
  • Enzyme Inhibitors / pharmacology*
  • Gelsolin / biosynthesis*
  • HeLa Cells
  • Humans
  • Lactones / pharmacology*
  • Macrolides
  • Mice
  • Microinjections
  • Oncogenes
  • Protein-Tyrosine Kinases / antagonists & inhibitors*


  • Enzyme Inhibitors
  • Gelsolin
  • Lactones
  • Macrolides
  • Cycloheximide
  • Protein-Tyrosine Kinases
  • monorden