INHIBITION OF CELLULAR GROWTH AND STEROID 11β-HYDROXYLATION IN RAS-TRANSFORMED ADRENOCORTICAL CELLS BY THE FUNGAL TOXINS BETICOLINS

The proliferation of GM16 and 4CDT ras-transformed newborn rat adrenocortical (RTAC) cells and Y1 mouse adrenal tumor cells was inhibited by beticolins, the fungal toxins extracted from Cercospora beticola, at submicromolar concentrations in a dose-dependent manner. Inhibitory concentrations for half the maximum inhibition were 150, 75 and 25 n Mfor beticolin-1 and 230, 150 and 50 n Mfor 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 μ M. 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.