Investigation of lactate calcium salt-induced beta-catenin destabilization in colorectal cancer cells

Abstract

Aims: Calcium supplements appear to reduce the risk of developing colorectal cancer (CRC), and it is necessary to clarify the mechanisms by which they exert their effects. In the present study, we investigate the supplementation effect of calcium via lactate calcium salt (CaLa) on CRC cells, focusing on beta-catenin destabilization. Main methods: The clonogenic assay was performed using different doses of CaLa. The expression level of c-Myc and Cyclin D1 was measured in addition to the confirmation of beta-catenin expression in the CRC cells. Glycogen synthase kinase (GSK)-3 beta expression was also confirmed in order to investigate the mechanism of beta-catenin degradation. Tumorigenic ability was confirmed using a xenograft animal model. Key findings: The number of colonies was significantly decreased after 2.5 mM CaLa treatment. CaLa-treated CRC cells showed a decrease in the beta-catenin expression. The quantitative level of the beta-catenin protein was significantly decreased in the CRC cell lysates, hence the expression level of c-Myc and cyclin D1 was significantly decreased following 2.5 mM CaLa treatment. We also confirmed that an increased expression of GSK-3 beta by CaLa is a key pathway in beta-catenin degradation. In the xenograft study, tumorigenicity was significantly inhibited to a maximum of 45% in the CaLa-treated group as compared with the control. Significance: These results support the idea that calcium supplementation via CaLa contributes to beta-catenin degradation and is hypothesized to reduce the risk of CRC. In addition, it indicates the possibility of CaLa being a potential incorporating agent with existing therapeutics against CRC. (C) 2015 Elsevier Inc. All rights reserved.