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 Ca ²⁺ 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 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 [Ca²⁺] _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 [Ca²⁺] _i rise. At 200-800 μM, 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 μM 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 Ca ²⁺ entry via store-operated Ca²⁺ channels. Caffeic acid also caused Ca²⁺-independent apoptosis.