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

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 β-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 β-catenin expression in the CRC cells. Glycogen synthase kinase (GSK)-3β expression was also confirmed in order to investigate the mechanism of β-catenin degradation. Tumorigenic ability was confirmed using a xenograft animal model.

KEY FINDINGS

The number of colonies was significantly decreased after 2.5mM CaLa treatment. CaLa-treated CRC cells showed a decrease in the β-catenin expression. The quantitative level of the β-catenin protein was significantly decreased in the CRC cell lysates, hence the expression level of c-Myc and cyclin D1 was significantly decreased following 2.5mM CaLa treatment. We also confirmed that an increased expression of GSK-3β by CaLa is a key pathway in β-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 β-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.