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

The proliferation of GM16 and 4CDT ins-transformed newborn rat adrenoc ortical (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 co ncentrations for half the maximum inhibition were 150, 75 and 25 nM fo r beticolin-1 and 230, 150 and 50 nM for beticolin-2 in GM16, 4CDT and Y1 cells respectively. Beticolins strongly inhibited the production o f 11 beta-hydroxysteroids on the second and third days of treatment il l a dose-dependent manner between 0.1 and 1 mu M. Beticolins were show n by confocal microscopy to be localized in cytoplasmic organelles abo ut 30-40 min after treatment. This finding favors a direct action of b eticolins on mitochondrial steroid 11 beta-hydroxylase albeit another less direct mechanism involving a cytoplasmic signaling pathway cannot be excluded. (C) 1996 Academic Press Limited