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.