The mechanism of NPC-14686-induced [Ca 2+ ] i rises and non-Ca 2+ -triggered cell death in MG63 human osteosarcoma cells

Jau Min Chien, Chiang Ting Chou, Wei Zhe Liang, Daih Huang Kuo, Chun Chi Kuo, Chin Man Ho, Pochuen Shieh*, Chung Ren Jan

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations


NPC-14686 has been shown to have anti-inflammatory effect in previous studies, but the mechanisms are unclear. The effect of NPC-14686 on cytosolic Ca 2+ concentrations ([Ca 2+ ] i ) and viability in MG63 human osteosarcoma cells was explored. The Ca 2+ -sensitive fluorescent dye fura-2 was applied to measure [Ca 2+ ] i . NPC-14686 at concentrations of 100-500 μM induced a [Ca 2+ ] i rise in a concentrationdependent manner. The response was reduced by 80% by removing Ca 2+ . NPC-14686 induced Mn 2+ influx leading to quenching of fura-2 fluorescence. NPC-14686-evoked Ca 2+ entry was suppressed by nifedipine, econazole, SK&F96365, and protein kinase C inhibitor. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca 2+ ] i rise. At 20-50 μM, NPC-14686 decreased cell viability, which was not reversed by chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that NPC-14686 (30-50 μM) induced apoptosis in a concentration-dependent manner. NPC-14686 also increased levels of reactive oxygen species. Together, in human osteosarcoma cells, NPC-14686 induced a [Ca 2+ ] i rise by inducing phospholipase C-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry via protein kinase C-sensitive store-operated Ca 2+ channels. NPC-14686 induced cell death that might involve apoptosis via mitochondrial pathways.

Original languageEnglish
Pages (from-to)158-166
Number of pages9
JournalChinese Journal of Physiology
Issue number3
StatePublished - 2014
Externally publishedYes


  • Apoptosis
  • Human osteosarcoma cells
  • NPC-14686


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