title: Effect of caffeic acid on Ca(2+) homeostasis and apoptosis in SCM1 human gastric cancer cells.
abstract: Caffeic acid is a natural phenolic compound that affects cellular Ca(2+) homeostasis and viability in different cells. This study examined the effect of caffeic acid on cytosolic free Ca(2+) concentrations ([Ca(2+)] i ) and viability in SCM1 human gastric cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)] i . Caffeic acid-evoked [Ca(2+)] i rises concentration dependently. The response was reduced by removing extracellular Ca(2+). Caffeic acid-evoked Ca(2+) entry was inhibited by store-operated channel inhibitors (nifedipine, econazole, and SK&F96365) and protein kinase C activator (phorbol 12-myristate 13 acetate, PMA), but not by protein kinase C inhibitor (GF109203X). In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished caffeic acid-evoked [Ca(2+)] i rise. Conversely, treatment with caffeic acid decreased thapsigargin or BHQ-evoked [Ca(2+)] i rise. Inhibition of phospholipase C with U73122 abolished caffeic acid-evoked [Ca(2+)] i rise. At 200-800 μM, caffeic acid inhibited 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). Caffeic acid between 400 and 800 μM also induced apoptosis. Collectively, in SCM1 cells, caffeic acid-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. Caffeic acid also caused Ca(2+)-independent apoptosis.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan.
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: I-Li
authors.initials: IL
authors.lastname: Chen
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.forename: Pochuen
authors.initials: P
authors.lastname: Shieh
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D017304:Annexin A5; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008345:Manganese / Q000378:metabolism; D011419:Propidium; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D002109:Caffeic Acids; D002614:Chelating Agents; D005456:Fluorescent Dyes; D011419:Propidium; D008345:Manganese; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2; C040048:caffeic acid