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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.
AuthorsSuxia Sun, Wenjun Li, He Zhang, Longying Zha, Yong Xue, Xianbo Wu, Fei Zou
JournalBioscience reports (Biosci Rep) Vol. 32 Issue 1 Pg. 83-90 (Feb 2012) ISSN: 1573-4935 [Electronic] England
PMID21699495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Boron Compounds
  • Butyrates
  • Chelating Agents
  • Imidazoles
  • Membrane Proteins
  • Neoplasm Proteins
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • 2-aminoethoxydiphenyl borate
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Calcium
Topics
  • Apoptosis (drug effects)
  • Boron Compounds (pharmacology)
  • Butyrates (pharmacology)
  • Calcium (metabolism)
  • Calcium Signaling
  • Cell Line, Tumor
  • Chelating Agents (pharmacology)
  • Colonic Neoplasms (drug therapy, metabolism, pathology)
  • Egtazic Acid (analogs & derivatives, pharmacology)
  • Endoplasmic Reticulum (drug effects, metabolism)
  • Humans
  • Imidazoles (pharmacology)
  • Membrane Proteins (genetics, metabolism)
  • Neoplasm Proteins (genetics, metabolism)
  • RNA Interference
  • Stromal Interaction Molecule 1

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