Effect of caffeic acid on Ca2+ homeostasis and apoptosis in SCM1 human gastric cancer cells

Caffeic acid is a natural phenolic compound that affects cellular Ca2+ homeostasis and viability in different cells. This study examined the effect of caffeic acid on cytosolic free Ca2+ concentrations ([Ca2+] (i) ) and viability in SCM1 human gastric cancer cells. The Ca2+-sensitive fluorescent dye fura-2 was used to measure [Ca2+] (i) . Caffeic acid-evoked [Ca2+] (i) rises concentration dependently. The response was reduced by removing extracellular Ca2+. Caffeic acid-evoked Ca2+ 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 Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished caffeic acid-evoked [Ca2+] (i) rise. Conversely, treatment with caffeic acid decreased thapsigargin or BHQ-evoked [Ca2+] (i) rise. Inhibition of phospholipase C with U73122 abolished caffeic acid-evoked [Ca2+] (i) rise. At 200-800 mu M, caffeic acid inhibited cell viability, which was not changed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Caffeic acid between 400 and 800 mu M also induced apoptosis. Collectively, in SCM1 cells, caffeic acid-induced [Ca2+] (i) rises by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via store-operated Ca2+ channels. Caffeic acid also caused Ca2+-independent apoptosis.