Effect of NPC-14686 (Fmoc-l-Homophenylalanine) on Ca(2)(+) Homeostasis and Viability in OC2 Human Oral Cancer Cells.

The effect of the anti-inflammatory compound NPC-14686 on intracellular Ca(2)(+) concentration ([Ca(2)(+)](i)) and viability in OC2 human oral cancer cells was investigated. The Ca(2)(+)-sensitive fluorescent probe fura-2 was used to examine [Ca(2)(+)](i). NPC-14686 induced [Ca(2)(+)](i) rises in a concentration-dependent fashion. The effect was reduced approximately by 10% by removing extracellular Ca(2)(+). NPC-14686- elicited Ca(2)(+) signal was decreased by nifedipine, econazole, SKF96365, and GF109203X. In Ca(2)(+)-free medium, incubation with the endoplasmic reticulum Ca(2)(+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished NPC-14686-induced [Ca(2)(+)](i) rises. Conversely, pretreatment with NPC-14686 abolished thapsigargin or BHQ-induced [Ca(2)(+)](i) rises. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca(2)(+)](i) rises. At 20-100 muM, NPC-14686 inhibited cell viability, which was not reversed by chelating cytosolic Ca(2)(+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid-acetoxymethyl ester (BAPTA/AM). NPC-14686 between 20 muM and 40 muM also induced apoptosis. Collectively, in OC2 cells, NPC-14686 induced [Ca(2)(+)](i) rises by evoking phospholipase C-dependent Ca(2)(+) release from the endoplasmic reticulum and Ca(2)(+) entry via protein kinase C-regulated store-operated Ca(2)(+) channels. NPC-14686 also caused Ca(2)(+)-independent apoptosis.