Nutr Res Pract.  2012 Oct;6(5):396-404.

Inhibitory effects of calcium against intestinal cancer in human colon cancer cells and ApcMin/+ mice

Affiliations
  • 1Department of Food and Nutrition, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju 361-763, Korea. jujih@chungbuk.ac.kr
  • 2Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.

Abstract

The aim of the study was to investigate the inhibitory effects of calcium against intestinal cancer in vitro and in vivo. We first investigated the effects of calcium treatment in HCT116 and HT29 human colon cancer cells. At the concentration range of 0.8-2.4 mM, calcium significantly inhibited cell growth (by 9-29%), attachment (by 12-26%), invasion (by 15-31%), and migration (by 19-61%). An immunofluorescence microscope analysis showed that the treatment with calcium (1.6 mM) for 24 h increased plasma membrane beta-catenin but decreased nuclear beta-catenin levels in HT29 cells. We then investigated the effect of dietary calcium on intestinal tumorigenesis in ApcMin/+ mice. Mice received dietary treatment starting at 6 weeks of age for the consecutive 8 weeks. The basal control diet contained high-fat (20% mixed lipids by weight) and low-calcium (1.4 mg/g diet) to mimic the average Western diet, while the treatment diet contained an enriched level of calcium (5.2 mg calcium/g diet). The dietary calcium treatment decreased the total number of small intestinal tumors (by 31.4%; P < 0.05). The largest decrease was in tumors which were > or = 2 mm in diameter, showing a 75.6% inhibition in the small intestinal tumor multiplicity (P < 0.001). Immunohistochemical analysis showed significantly reduced nuclear staining of beta-catenin (expressed as nuclear positivity), but increased plasma membrane staining of beta-catenin, in the adenomas from the calcium-treated groups in comparison to those from the control group (P < 0.001). These results demonstrate intestinal cancer inhibitory effects of calcium both in human colon cancer cells and Apc Min/+ mice. The decreased beta-catenin nuclear localization caused by the calcium treatment may contribute to the inhibitory action.

Keyword

Calcium; human colon cancer cells; ApcMin/+ mice; beta-catenin
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