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

10.4077/CJP.2015.BAD311

Yih-Do Li；Chiang-Ting Chou；Wei-Zhe Liang；Hui-Wen Tseng；Yi-Chien Fang；Tzu-Yi Hung；Hong-Tai Chang；Daih-Huang Kuo；Chun-Chi Kuo；Chin-Man Ho；Pochuen Shieh；Fu-An Chen；Chung-Ren Jan

Apoptosis ； Ca^(2+) ； endoplasmic reticulum ； human oral cancer cells ； NPC-14686 ； phospholipase C

The Chinese Journal of Physiology

58卷5期（2015 / 10 / 31）

285 - 293

英文

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 Ca2+-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 μM, 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 μM and 40 μM 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.

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