Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation
- 199 Downloads
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.
KeywordsCalcium Gadolinium Colon Differentiation Cytotoxicity
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.
- 4.McCullough ML, Robertson AS, Rodriguez C, Jacobs EJ, Chao A, Carolyn J, Calle EE, Willett WC, Thun MJ (2003) Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). Cancer Causes Control 14:1–12PubMedCrossRefGoogle Scholar
- 11.Behrens J, Vakaet L, Friis R, Winterchger E, van Roy F, Mareel MM, Birchmeier W (1992) Loss of epithelial differentiation and gain of invasiveness correlates with tryrosine phosphorylation of the E-cadherin/β-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol 120:757–766CrossRefGoogle Scholar
- 18.Bostick RM, Goodman M, Sidelnikov E (2009) Calcium and vitamin D. In: Potter JD, Lindor NM (eds) Genetics of colorectal cancer. Springer, New York, pp 273–294Google Scholar
- 19.Aslam MN, Bergin I, Naik M, Hampton A, Rehman M, Dame MK, Rush H, Varani J (2012) A multi-mineral natural product from red marine algae reduces colon polyp formation in C57BL/6 mice. Nutr Cancer 64(7). doi: 10.1080/01635581.2012.713160
- 20.Evans CH (ed) (1990) Biochemistry of the lanthanides. In: Biochemistry of the elements. Plenum, New YorkGoogle Scholar
- 21.Gschneidner KA Jr, Eyring L (eds) (2000) Handbook on the physics and chemistry of rare earths. Elsevier, AmsterdamGoogle Scholar
- 35.Liu G, Hu X, Premkumar L, Chakrabarty S (2011) Nifedipine synergizes with calcium in activating the calcium sensing receptor, suppressing the expression of thymidylate synthase and survivin and promoting sensitivity to fluorouracil in human colon carcinoma cells. Mol Carcinog 50:922–930PubMedCrossRefGoogle Scholar