title: Effect of NPC-14686 (Fmoc-l-Homophenylalanine) on Ca²⁺ Homeostasis and Viability in OC2 Human Oral Cancer Cells.
abstract: The effect of the anti-inflammatory compound NPC-14686 on intracellular Ca²⁺ concentration ([Ca²⁺](i)) and viability in OC2 human oral cancer cells was investigated. The Ca²⁺-sensitive fluorescent probe fura-2 was used to examine [Ca²⁺](i). NPC-14686 induced [Ca²⁺](i) rises in a concentration-dependent fashion. The effect was reduced approximately by 10% by removing extracellular Ca²⁺. NPC-14686- elicited Ca²⁺ signal was decreased by nifedipine, econazole, SKF96365, and GF109203X. In Ca²⁺-free medium, incubation with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished NPC-14686-induced [Ca²⁺](i) rises. Conversely, pretreatment with NPC-14686 abolished thapsigargin or BHQ-induced [Ca²⁺](i) rises. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca²⁺](i) rises. At 20-100 μM, NPC-14686 inhibited cell viability, which was not reversed by chelating cytosolic Ca²⁺ 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 [Ca²⁺](i) rises by evoking phospholipase C-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via protein kinase C-regulated store-operated Ca²⁺ channels. NPC-14686 also caused Ca²⁺-independent apoptosis.
authors.affiliation: Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung 81345, Taiwan, Republic of China.
authors.forename: Yih-Do
authors.initials: YD
authors.lastname: Li
authors.affiliation: Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan, Republic of China.|Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan, Republic of China.
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.affiliation: Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Tseng
authors.affiliation: Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung 81345, Taiwan, Republic of China.
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Fang
authors.affiliation: Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung 81345, Taiwan, Republic of China.
authors.forename: Tzu-Yi
authors.initials: TY
authors.lastname: Hung
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.affiliation: Department of Nursing, Tzu Hui Institute of Technology, Pingtung 92641, Taiwan, Republic of China.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
authors.forename: Chin-Man
authors.initials: CM
authors.lastname: Ho
authors.affiliation: Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
authors.forename: Pochuen
authors.initials: P
authors.lastname: Shieh
authors.affiliation: Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Chen
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004721:Endoplasmic Reticulum / Q000378:metabolism; D016257:Fura-2; D006706:Homeostasis; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000613:Aminobutyrates; D015220:Calcium Channels; C417979:NPC 14686; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2