title: Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells.
abstract: 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.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University Guangzhou, Guangdong, People's Republic of China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Sun
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Longying
authors.initials: L
authors.lastname: Zha
authors.forename: Yong
authors.initials: Y
authors.lastname: Xue
authors.forename: Xianbo
authors.initials: X
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D000071737:Stromal Interaction Molecule 1
chemical_list: D001896:Boron Compounds; D002087:Butyrates; D002614:Chelating Agents; D007093:Imidazoles; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C109986:2-aminoethoxydiphenyl borate; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium