Previous murine studies have demonstrated that dietary Aquamin®, a calcium-rich, multi-mineral natural product, suppressed colon polyp formation and transition to invasive tumors more effectively than calcium alone when provided over the lifespan of the animals. In the present study, we compared calcium alone to Aquamin® for modulation of growth and differentiation in human colon adenomas in colonoid culture. Colonoids established from normal colonic tissue were examined in parallel. Both calcium alone at 1.5 mM and Aquamin® (provided at 1.5 mM calcium) fostered differentiation in the adenoma colonoid cultures as compared to control (calcium at 0.15 mM). When Aquamin® was provided at an amount delivering 0.15 mM calcium, adenoma differentiation also occurred, but was not as complete. Characteristic of colonoids undergoing differentiation was a reduction in the number of small, highly-proliferative buds and their replacement by fewer but larger buds with smoother surface. Proliferation marker (Ki67) expression was reduced and markers of differentiation (CK20 and Occludin) were increased along with E-cadherin translocalization to the cell surface. Additional proteins associated with differentiation / growth control (including histone-1 family members, certain keratins, NF-2 [merlin], olfactomedin-4 and metallothionines) were altered as assessed by proteomics. Immunohistological expression of NF-2 was higher with Aquamin® as compared to calcium at either concentration. These findings support the conclusions that i) calcium (1.5 mM) has the capacity to modulate growth and differentiation in large human colon adenomas and ii) Aquamin® delivering 0.15 mM calcium has effects on proliferation and differentiation not observed when calcium is used alone at this concentration.
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