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

Authors

  • GUOQING DING,

    1. Unité associée INRA-Université 692, Phytopharmacie et Biochimie des Interactions Cellulaires, Université de Bourgogne, BP 138, 21004 Dijon Cedex, France
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  • GABRIELLE MAUME,

    1. Unité associée INRA-Université 692, Phytopharmacie et Biochimie des Interactions Cellulaires, Université de Bourgogne, BP 138, 21004 Dijon Cedex, France
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  • MARIE-LOUISE MILAT,

    1. Unité associée INRA-Université 692, Phytopharmacie et Biochimie des Interactions Cellulaires, Université de Bourgogne, BP 138, 21004 Dijon Cedex, France
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  • CLAUDE HUMBERT,

    1. Unité associée INRA-Université 692, Phytopharmacie et Biochimie des Interactions Cellulaires, Université de Bourgogne, BP 138, 21004 Dijon Cedex, France
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  • JEAN-PIERRE BLEIN,

    1. Unité associée INRA-Université 692, Phytopharmacie et Biochimie des Interactions Cellulaires, Université de Bourgogne, BP 138, 21004 Dijon Cedex, France
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  • BERNARD F. MAUME

    Corresponding author
    1. Unité associée INRA-Université 692, Phytopharmacie et Biochimie des Interactions Cellulaires, Université de Bourgogne, BP 138, 21004 Dijon Cedex, France
      To whom correspondence should be addressed.
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To whom correspondence should be addressed.

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.

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