Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor

The Journal of Steroid Biochemistry and Molecular Biology
Abhishek AggarwalE Kállay

Abstract

Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes. However, during tumorigenesis colonic CaSR expression is downregulated and we hypothesized that the loss of CaSR could influence the anti-tumorigenic effects of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg diet) increased expression of differentiation and apoptosis markers, decreased expression of proliferation markers and significantly upregulated CaSR mRNA expression, compared with low vitamin D diet (100 IU/kg diet). To determine the role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated them with 1,25-D3 alone, or in combination with CaSR ac...Continue Reading

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Citations

Apr 29, 2016·Journal of Cellular Biochemistry·Elżbieta Gocek, George P Studzinski
Nov 3, 2016·Frontiers in Physiology·Abhishek Aggarwal, Enikö Kállay
Feb 17, 2017·Future Medicinal Chemistry·Pawin PongkorpsakolChatchai Muanprasat
Mar 28, 2018·International Journal of Molecular Sciences·Andrea Gerbino, Matilde Colella
Aug 16, 2018·The British Journal of Nutrition·Guangmang LiuJing Wang
Jan 1, 2017·Journal of Cancer Prevention & Current Research·Karen L ChenZeynep Madak-Erdogan
Aug 29, 2020·Cancers·Asunción Fernández-BarralAlberto Muñoz
Apr 24, 2018·BioMed Research International·Fang HeYuanyi Peng
Dec 5, 2018·Digestive Diseases and Sciences·Hemant GoyalGiuseppe Lippi
Oct 3, 2018·World Journal of Gastroenterology : WJG·Luca IamartinoMartin Schepelmann
Aug 31, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Luca IamartinoEnikö Kallay

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