Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells

The SOCE (store-operated Ca 2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca 2+ signalling. In this paper, we provide evidence that butyric acid, a dietary fibre-derived short-chain fatty acid, induces apoptosis of colon cancer cells via SOCE signalling networks. We found that sodium butyrate (NaB) induces Ca 2+ release from endoplasmic reticulum, which in turn causes extracellular Ca 2+ influx in HCT-116 cells. The Ca 2+ release and influx are important, because the addition of chelators, EGTA or BAPTA/AM [1,2-bis-( o -aminophenoxy)ethane- N , N , N ′, N ′-tetra-acetic acid tetrakis(acetoxymethyl ester)] respectively blocked NaB-induced apoptosis. Furthermore, down-regulation of STIM1 (stromal interaction molecule 1) by RNA interference or pharmacological blockade of the SOCC (store-operated Ca 2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca 2+ influx and apoptosis in HCT-116 cells. Thus we conclude that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. This finding provides new insights into how butyric acid suppresses colon carcinogenesis.