Resistance of store‐operated calcium entry to tumour microenvironment conditions and enhanced potency of Synta66 in colorectal adenocarcinoma cells (1057.4)

Abstract

Store‐operated CRAC (SOC) channels have been suggested as drivers of tumour expansion. The aim of this study was to determine the effectiveness of a putatively specific SOC channel inhibitor (Synta66) in tumour microenvironment conditions. Cytoplasmic calcium concentration in HT‐29 colorectal adenocarcinoma cells was measured using a 96‐well plate fluorometer and the calcium indicator fura‐2. Hydrogen peroxide (1 µM‐1 mM), arachidonic acid (1 µM‐50 µM) and pH range 6.4‐7.4 were used as examples of common tumour microenvironment conditions. Contrary to expectations from studies of other cell types, hydrogen peroxide and arachidonic acid had no effect on SOC‐mediated calcium entry. pH 6.8 caused partial inhibition. The calcium entry was readily detected in the combined presence of all three conditions. Synta66 inhibited the calcium entry and was more potent in the presence of hydrogen peroxide, arachidonic acid or pH 6.8. The data support the hypothesis that chemical inhibitors of SOC channels may be useful for tumour suppression.Grant Funding Source: Supported by the British Heart Foundation, Cancer Research UK, and the Medical Research Council.