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. β-Carotene (100 nM to 100 μM), 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 thetrans configuration. β-Carotene strongly suppressed the hyperphosphorylation of cellular proteins induced by microcystin-LR without significant changes in the basal phosphorylation level. Other antioxidants, such as α-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.
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Abbreviations
- DMSO:
-
dimethylsulfoxide
- THF:
-
tetrahydrofuran
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Matsushima-Nishiwaki, R., Shidoji, Y., Nishiwaki, S. et al. Suppression by carotenoids of microtenoids of microcystin-induced morphological changes in mouse hepatocytes. Lipids 30, 1029–1034 (1995). https://doi.org/10.1007/BF02536288
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DOI: https://doi.org/10.1007/BF02536288