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Chin J Physiol. 2016 Oct 31;59(5):268-275. doi: 10.4077/CJP.2016.BAF421.

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

Author information

1
Department of Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua 50544, Taiwan, Republic of China.
2
Department of Nursing, Division of Basic Medical Sciences, Chang Gung Institute of Technology, Chia-Yi 61363, Taiwan, Republic of China.
3
Chronic Diseases and Health Promotion Research Center, Chang Gung Institute of Technology, Chia-Yi 61363, Taiwan, Republic of China.
4
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
5
Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
6
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
7
Department of Nursing, Tzu Hui Institute of Technology, Pingtung 92641, Taiwan, Republic of China.
8
Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
9
Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.

Abstract

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.

KEYWORDS:

Ca²⁺; NPC15199; endoplasmic reticulum; fura-2; gastric cancer cells

PMID:
27604137
DOI:
10.4077/CJP.2016.BAF421
[Indexed for MEDLINE]

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