Exploration of niflumic acid’s action on Ca 2+ movement and cell viability in human osteosarcoma cells

Wei Chuan Liao, Chiang Ting Chou, Wei Zhe Liang, Lyh Jyh Hao, Chun Chi Kuo, Ko Long Lin*, Jue Long Wang, Chung Ren Jan

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

3 引文 斯高帕斯(Scopus)

摘要

Niflumic acid, a drug used for joint and muscular pain, affected Ca 2+ signaling in different models. However, the effect of niflumic acid on Ca 2+ homeostasis and Ca 2+ -related physiology in human osteosarcoma cells is unknown. This study examined the effect of niflumic acid on cytosolic free Ca2+ concentrations ([Ca2+]i) in MG63 human osteosarcoma cells. Intracellular Ca2+ concentrations in suspended cells were monitored by using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). In MG63 cells, niflumic acid at concentrations of 250-750 µM evoked [Ca2+]i rises concentration-dependently. Niflumic acid-evoked Ca2+ entry was confirmed by Mn2+-induced quenching of fura-2 fluorescence. This entry was inhibited by nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA), but was not affected by the PKC inhibitor GF109203X. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) inhibited niflumic acid-evoked [Ca2+]i rises. Conversely, treatment with niflumic acid abolished TG-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 also partly reduced niflumic acid-evoked [Ca 2+ ] i rises. Niflumic acid killed cells at 200-500 μM in a concentration-dependent fashion. Chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid/ AM (BAPTA/AM) did not reverse niflumic acid-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, niflumic acid induced [Ca 2+ ] i rises by evoking PLC-dependent Ca 2+ release from the endoplasmic reticulum, and Ca 2+ entry via PKC-sensitive store-operated Ca 2+ entry. Niflumic acid also induced Ca 2+ -independent cell death.

原文英語
頁(從 - 到)341-348
頁數8
期刊Chinese Journal of Physiology
61
發行號6
DOIs
出版狀態已出版 - 2018
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©2018 by The Chinese Physiological Society.

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