Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University Guangzhou, Guangdong, People's Republic of China.
Biosci Rep. 2012 Feb;32(1):83-90. doi: 10.1042/BSR20110062.
The SOCE (store-operated Ca2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca2+ 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 Ca2+ release from endoplasmic reticulum, which in turn causes extracellular Ca2+ influx in HCT-116 cells. The Ca2+ 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 Ca2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca2+ 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.
SOCE（储存操作的钙进入）途径在正常细胞和癌细胞中都起着关键作用。然而，其分子机制仍然是钙信号转导的一个长期存在的难题。在本文中，我们提供了证据表明，丁酸，一种膳食纤维衍生的短链脂肪酸，通过 SOCE 信号网络诱导结肠癌细胞凋亡。我们发现，丁酸钠（NaB）诱导内质网钙释放，进而导致 HCT-116 细胞外钙内流。钙释放和内流很重要，因为螯合剂 EGTA 或 BAPTA/AM[1,2-双（邻氨基苯氧基）乙烷-N，N，N'，N'-四乙酸四（乙酰氧甲基）酯]的添加分别阻断了 NaB 诱导的细胞凋亡。此外，RNA 干扰下调 STIM1（基质相互作用分子 1）或 2-APB（2-氨基乙氧基二苯硼酸盐）或 SKF-96365 药理学阻断 SOCC（储存操作的钙通道）抑制了 HCT-116 细胞中 NaB 诱导的细胞外钙内流和凋亡。因此，我们得出结论，NaB 以 SOCE 依赖的方式触发结肠癌细胞凋亡。这一发现为丁酸如何抑制结肠癌发生提供了新的见解。
