PMID- 16127738 OWN - NLM STAT- MEDLINE DCOM- 20051219 LR - 20190430 IS - 1007-9327 (Print) IS - 2219-2840 (Electronic) IS - 1007-9327 (Linking) VI - 11 IP - 33 DP - 2005 Sep 7 TI - Bile salts inhibit growth and induce apoptosis of human esophageal cancer cell line. PG - 5109-16 AB - AIM: To explore the effect of six bile salts, including glycocholate (GC), glycochenodeoxycholate (GCDC), glycodeoxycholate (GDC), taurocholate (TC), taurochenodeoxycholate (TCDC), taurodeoxycholate (TDC), and two bile acids including cholic acid (CA) and deoxycholic acid (DCA) on esophageal cancer Eca109 cell line. METHODS: Eca109 cells were exposed to six bile salts, two bile acids and the mixed bile salts at different concentrations for 24-72 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to detect the cell proliferation. Apoptotic morphology was observed by phase-contrast video microscopy and deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Sub-G1 DNA fragmentations and early apoptosis cells were assayed by flow cytometry (FCM) with propidium iodide (PI) staining and annexin V-FITC conjugated with PI staining. Apoptosis DNA ladders on agarose were observed. Activation of caspase-3 was assayed by FCM with FITC-conjugated monoclonal rabbit anti-active caspase-3 antibody and expressions of Bcl-2 and Bax proteins were examined immunocytochemically in 500 micromol/L-TC-induced apoptosis cells. RESULTS: Five bile salts except for GC, and two bile acids and the mixed bile salts could initiate growth inhibition of Eca109 cells in a dose- and time-dependent manner. TUNEL, FCM, and DNA ladder assays all demonstrated apoptosis induced by bile salts and bile acids at 500 micromol/L, except for GC. Early apoptosis cell percentages in Eca109 cells treated with GCDC, GDC, TC, TCDC, TDC, CA at 500 micromol/L for 12 h, DCA at 500 micromol/L for 6 h, and mixed bile salts at 1000 micromol/L for 12 h were 7.5%, 8.7%, 14.8%, 8.9%, 7.8%, 9.3%, 22.6% and 12.5%, respectively, all were significantly higher than that in control (1.9%). About 22% of the cell population treated with TC at 500 micromol/L for 24 h had detectable active caspase-3, and were higher than that in the control (1%). Immunocytochemical assay suggested that TC down-regulated Bcl-2 protein level and up-regulated Bax protein level. CONCLUSION: GCDC, GDC, TC, TCDC, TDC, CA and DCA, except for GC, can inhibit growth and induce apoptosis of esophageal cancer Eca109 cells. Activation of caspase-3, decreased Bcl-2 protein and increased Bax protein are involved in TC-induced apoptosis of Eca109 cells. FAU - Zhang, Ru AU - Zhang R AD - Digestive Department of the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. FAU - Gong, Jun AU - Gong J FAU - Wang, Hui AU - Wang H FAU - Wang, Li AU - Wang L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Bile Acids and Salts) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) SB - IM MH - Apoptosis/*drug effects MH - Bile Acids and Salts/*pharmacology MH - Caspase 3 MH - Caspases/metabolism MH - Cell Division/drug effects MH - Cell Line, Tumor MH - Enzyme Activation MH - Esophageal Neoplasms/metabolism/*pathology/*physiopathology MH - Humans MH - Proto-Oncogene Proteins c-bcl-2/metabolism PMC - PMC4320381 EDAT- 2005/08/30 09:00 MHDA- 2005/12/20 09:00 PMCR- 2005/09/07 CRDT- 2005/08/30 09:00 PHST- 2005/08/30 09:00 [pubmed] PHST- 2005/12/20 09:00 [medline] PHST- 2005/08/30 09:00 [entrez] PHST- 2005/09/07 00:00 [pmc-release] AID - 10.3748/wjg.v11.i33.5109 [doi] PST - ppublish SO - World J Gastroenterol. 2005 Sep 7;11(33):5109-16. doi: 10.3748/wjg.v11.i33.5109.