Suppression by Carotenoids of Microcystin-Induced Morphological Changes in Mouse Hepatocytes

Lipids. 1995 Nov;30(11):1029-34. doi: 10.1007/BF02536288.

Abstract

Microcystin-LR is a liver tumor promoter in the okadaic acid class, a group of potent inhibitors of protein phosphatases 1 and 2A. Because of inhibition of protein phosphatases, microcystin-LR induces hyperphosphorylation of cellular proteins, including cytoskeletal proteins--cytokeratins 8 and 18--and causes morphological changes in mouse hepatocytes in primary culture. We studied the effects of carotenoids to antagonize microcystin-LR-induced morphological changes in hepatocytes. beta-carotene (100 nM to 100 microns) suppressed the morphological changes induced by 100 nM microcystin-LR in a dose-dependent manner. Other carotenoids tested exerted similar suppressive effects, although retinoids, such as all-trans retinol, all-trans retinoic acid, and 9-cis retinoic acid, were only weakly suppressive. The relative potency of the suppression correlated significantly with the number of conjugated double bonds in the trans configuration. beta-carotene strongly suppressed the hyperphosphorylation of cellular proteins induced by microcystin-LR without significant changes in the basal phosphorylation level. Other antioxidants, such as alpha-tocopherol, did not protect the cells against microcystin-LR. Taken together, the antagonistic effects of carotenoids against microcystin-LR are difficult to explain by their antioxidant or provitamin A activities. Suppression of the hyperphosphorylation of cellular proteins may be a novel mechanism by which carotenoids inhibit tumor promotion.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Carotenoids / pharmacology*
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Fluorescent Antibody Technique, Indirect
  • Liver / cytology*
  • Liver / drug effects*
  • Lutein / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microcystins
  • Peptides, Cyclic / pharmacology*
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphorylation
  • Retinoids / pharmacology
  • beta Carotene

Substances

  • Antioxidants
  • Cytoskeletal Proteins
  • Enzyme Inhibitors
  • Microcystins
  • Peptides, Cyclic
  • Retinoids
  • beta Carotene
  • Carotenoids
  • microcystin
  • Phosphoprotein Phosphatases
  • Lutein