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Zinc increased the sensitivity of HepG2 and AML12 cells towards retinoic acid‐mediated growth inhibition
Author(s) -
Ibbitson Deanna,
Xu Zhaoming
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb257
Subject(s) - retinoic acid , zinc , retinoic acid receptor , cell growth , retinoid , chemistry , tretinoin , cell cycle , cell , biochemistry , biology , medicine , organic chemistry , gene
Retinoic acid has been shown to reduce cell growth by interrupting cell cycle. This effect of retinoic acid involves retinoic acid receptor and retinoid X receptor, two zinc‐finger proteins. We hypothesized that the sensitivity of cells towards retinoic acid‐mediated growth inhibition can be modulated by zinc status. To test this hypothesis, hepatoma HepG2 cells were cultured in a low‐zinc media supplemented with 0 (low‐zinc group), 5 (adequate‐zinc group), and 10 (zinc‐supplemented group) μM of zinc followed by treating the cells with retinoic acid at 0 and 35 μM. Culturing the cells in the low‐zinc media depleted the labile intracellular pool of zinc by 86% while the total cellular zinc concentration was reduced by 28%. Treating the cells with retinoic acid reduced cell proliferation in the low‐zinc, adequate‐zinc, and zinc‐supplemented group by 36, 49, and 55%, respectively. Cell cycle analysis showed that retinoic acid treatment reduced the number of cells in the S‐phase in the adequate‐zinc and zinc‐supplemented groups by 27% compared to the low‐zinc group. Similar effects were obtained in normal hepatocyte AML12 cells using the same treatment regime. Collectively, these results suggested that zinc supplementation sensitized HepG2 and AML12 cells towards retinoic acid‐mediated growth inhibition. Supported by the Vitamin Research Fund .