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 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 nM for beticolin-1 and 230, 150 and 50 nM for beticolin-2 in GM16, 4CDT and Y1 cells respectively. Beticolins strongly inhibited the production of 11 beta-hydroxysteroids on the second and third days of treatment in a dose-dependent manner between 0.1 and 1 microM. 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 11 beta-hydroxylase albeit another less direct mechanism involving a cytoplasmic signaling pathway cannot be excluded.
Ding
G
G
Unité associée INRA-Université 692, Université de Bourgogne, Dijon, France.
Maume
G
G
Milat
M L
ML
Humbert
C
C
Blein
J P
JP
Maume
B F
BF
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D011905:Genes, ras; D006131:Growth Inhibitors / Q000494:pharmacology*; D006576:Heterocyclic Compounds, 4 or More Rings; D006914:Hydroxysteroids / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D009183:Mycotoxins / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D006914:Hydroxysteroids; D009183:Mycotoxins; D009363:Neoplasm Proteins; C089994:beticolin 2; C089993:beticolin 1; D013252:Steroid 11-beta-Hydroxylase