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 μM 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.
Department of Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua 50544, Taiwan, Republic of China.
He-Hsiung
HH
Cheng
Department of Nursing, Division of Basic Medical Sciences, Chang Gung Institute of Technology, Chia-Yi 61363, Taiwan, Republic of China.|Chronic Diseases and Health Promotion Research Center, Chang Gung Institute of Technology, Chia-Yi 61363, Taiwan, Republic of China.
Chiang-Ting
CT
Chou
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
Wei-Zhe
WZ
Liang
Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
Jin-Shiung
JS
Cheng
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
Hong-Tai
HT
Chang
Department of Nursing, Tzu Hui Institute of Technology, Pingtung 92641, Taiwan, Republic of China.
Chun-Chi
CC
Kuo
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
I-S
IS
Chen
Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
Ti
T
Lu
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
C-C
CC
Yu
Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
Fu-An
FA
Chen
Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
Daih-Huang
DH
Kuo
Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
Pochuen
P
Shieh
Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
Chung-Ren
CR
Jan
D020013:Calcium Signaling / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005449:Fluorenes / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy*; D010738:Type C Phospholipases / Q000378:metabolism
D005449:Fluorenes; C082231:N-(fluorenyl-9-methoxycarbonyl)leucine; D010738:Type C Phospholipases; D007930:Leucine
Ca²⁺; NPC15199; endoplasmic reticulum; fura-2; gastric cancer cells