Effect of NPC15199 on [Ca²⁺]i and viability in SCM1 human gastric cancer cells.

NPC15199 is a synthesized compound that inhibits inflammation in some models. However, whether NPC15199 affects Ca2+ homeostasis in human gastric cancer is unclear. This study examined the effect of NPC15199 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). NPC15199 evoked [Ca2+](i) rises concentration-dependently. The response was reduced by removing extracellular Ca2+. NPC15199-evoked Ca2+ entry was not inhibited by store-operated channel inhibitors (nifedipine, econazole and SKF96365) and protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA), or PKC inhibitor (GF109203X). In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished NPC15199-evoked [Ca2+](i) rises. Conversely, treatment with NPC15199 also nearly abolished thapsigargin or BHQ-evoked [Ca2+](i) rises. Inhibition of phospholipase C (PLC) with U73122 did not affect NPC15199-evoked [Ca2+](i) rises. NPC15199 at concentrations of 100-900 mu M induced concentration-dependent, Ca2+-independent decrease in viability. Together, in SCM1 cells, NPC15199 induced [Ca2+]i rises that involved Ca2+ entry through PKC-insensitive non-store-operated Ca2+ channels and PLC-independent Ca2+ release from the endoplasmic reticulum. NPC15199 also induced Ca2+-independent cell death.