title: Effect of deoxycholic acid on Ca2+ movement, cell viability and apoptosis in human gastric cancer cells.
abstract: Deoxycholic acid (DOA) is one of the secondary bile acids used as a mild detergent for the isolation of membrane associated proteins. This study examined whether the secondary bile acid, DOA, altered Ca(2+) movement, cell viability and apoptosis in SCM1 human gastric cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i. DOA-evoked [Ca(2+)]i rises concentration dependently. The response was reduced by removing extracellular Ca(2+). DOA-evoked Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (nifedipine, econazole and SKF96365), the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA) and the PKC inhibitor GF109203X. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) abolished DOA-evoked [Ca(2+)]i rises. Conversely, treatment with DOA abolished TG-evoked [Ca(2+)]i rises. Inhibition of phospholipase C with U73122 abolished DOA-evoked [Ca(2+)]i rises. At 100-500 μM, DOA decreased cell viability, which was not changed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). DOA between 100 and 300 μM also induced apoptosis. Collectively, in SCM1 cells, DOA-induced [Ca(2+)]i rises by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. DOA also caused Ca(2+)-independent apoptosis.
authors.affiliation: Department of Pediatrics, Ping Tung Christian Hospital , Ping Tung , Taiwan .
authors.forename: Jau-Min
authors.initials: JM
authors.lastname: Chien
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Jin-Shiung
authors.initials: JS
authors.lastname: Cheng
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Tseng
authors.forename: Soong-Yu
authors.initials: SY
authors.lastname: Kuo
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Chen
authors.forename: Pochuen
authors.initials: P
authors.lastname: Shieh
authors.forename: Chin-Man
authors.initials: CM
authors.lastname: Ho
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Lin
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D065096:Calcium Chelating Agents / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D065096:Calcium Chelating Agents; D020536:Enzyme Activators; D047428:Protein Kinase Inhibitors; D003840:Deoxycholic Acid; C049925:fura-2-am; D011493:Protein Kinase C; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2
keywords: Apoptosis; Ca2+; deoxycholic acid; endoplasmic reticulum; gastric cancer cells