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

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.

Calcium-Induced Differentiation of Human Colon Adenomas in Colonoid Culture: Calcium Alone versus Calcium with Additional Trace Elements

“…How the combination of trace elements and calcium in Aquamin ® promotes differentiation at the low overall calcium concentration is not fully understood. Several different trace elements represented in the natural product (including members of the lanthanide family) bind to proteins involved in calcium signaling/mobilization (41–45). One of these, the extracellular calcium sensing receptor, plays a critical role in growth-regulating responses to calcium in the colon (46).…”

Differentiation of human colon tissue in culture: Effects of calcium on trans-epithelial electrical resistance and tissue cohesive properties

“…What accounts for the enhanced response to the multi-mineral intervention is not known with certainty, but previous studies provide insight. Aquamin itself, as well as certain of the individual trace elements present in the multi-mineral product, activate the extracellular calciumsensing receptor, a critical target in epithelial cell responses to calcium, more effectively than calcium itself [50][51][52]. In the presence of the additional trace elements, a "left-shift" in calcium response occurs.…”

Proteins and Carbohydrates from Red Seaweeds: Evidence for Beneficial Effects on Gut Function and Microbiota

“…Although calcium may be in part responsible for the observed effects, some of the trace elements (lanthanides in particular) have been proposed to enhance the growth control properties of calcium. In this sense, it has been shown that gadolinium increases the growth inhibitory properties of calcium on intestinal epithelial cells, without affecting calcium-induced differentiation [ 100 ]. Mechanisms involved in this effect remain to be elucidated.…”