SEARCH

SEARCH BY CITATION

Keywords:

  • adrenocortical cell;
  • rasoncogene transformation;
  • Cercospora beticolatoxins;
  • growth inhibition;
  • steroid biosynthesis inhibition;
  • laser confocal microscopy

Abstract

The proliferation of GM16 and 4CDTras-transformed newborn rat adrenocortical (RTAC) cells and Y1 mouse adrenal tumor cells was inhibited by beticolins, the fungal toxins extracted fromCercospora beticola, at submicromolar concentrations in a dose-dependent manner. Inhibitory concentrations for half the maximum inhibition were 150, 75 and 25 nmfor beticolin-1 and 230, 150 and 50 nmfor beticolin-2 in GM16, 4CDT and Y1 cells respectively. Beticolins strongly inhibited the production of 11β-hydroxysteroids on the second and third days of treatment in a dose-dependent manner between 0.1 and 1 μm. Beticolins were shown by confocal microscopy to be localized in cytoplasmic organelles about 30–40 min after treatment. This finding favors a direct action of beticolins on mitochondrial steroid 11β-hydroxylase albeit another less direct mechanism involving a cytoplasmic signaling pathway cannot be excluded.