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Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation

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Abstract

Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1–5 μM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

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Acknowledgments

This study was supported in part by grant CA140760 from the National Institutes of Health, Bethesda, MD and by grant 11–0577 from the Association for International Cancer Research, St. Andrews, Fife, Scotland.

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  1. Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, SPC 5602, Ann Arbor, MI, 48109, USA

    Durga Attili, Brian Jenkins, Muhammad Nadeem Aslam, Michael K. Dame & James Varani

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  1. Durga Attili
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  2. Brian Jenkins
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  3. Muhammad Nadeem Aslam
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Correspondence to James Varani.

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Attili, D., Jenkins, B., Aslam, M.N. et al. Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation. Biol Trace Elem Res 150, 467–476 (2012). https://doi.org/10.1007/s12011-012-9503-9

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