NPC-14686 (Fmoc-l-homophenylalanine)-induced Ca2+ increases and death in human prostate cancer cells

Huang, Jong‐Khing; Liu, Chung-Shin; Chen, Wei‐Chuan; Liu, Shiuh–Inn; Hsu, Shu-Shong; Chang, Hong‐Tai; Chou, Chiang-Ting; Hsieh, Ching-Hong; Chang, Chih-Hung; Jan, Chung‐Ren

doi:10.1016/j.lfs.2005.06.018

Cited by 1 publication

(2 citation statements)

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“…However, an unregulated [Ca 2+ ] i rise may cause cell death via apoptosis (1,8). Previous studies showed that NPC-14686 increased intracellular free Ca 2+ levels in human hepatoma cells (13) and canine renal tubular cells (14), and caused cell death in human prostate cancer cells (11). Although NPC-14686 induced [Ca 2+ ] i rises and caused cytotoxicity in different cancer cells, whether NPC-14686 could increase [Ca 2+ ] i and evoke death in osteosarcoma cells is unknown.…”

Section: Introductionmentioning

confidence: 99%

“…NPC-14686 (Fmoc-l-homophenylalanine) is one of these compounds and has been shown to prevent gastric mucosal lesions in rats (20). Previous Effect of NPC-14686 on Human Osteosarcoma Cells 159 studies showed that NPC-14686 induced intracellular Ca 2+ concentration ([Ca 2+ ] i ) rises and caused cell death in different cancer cells such as human prostate cancer cells (11) and human hepatoma cells (13). Collectively, NPC-14686 caused cytotoxicity in different cancer cells, but the underlying mechanisms are not clear.…”

Section: Introductionmentioning

confidence: 99%

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The Mechanism of NPC-14686-Induced [Ca^(2+)]i Rises and Non-Ca^(2+)-Triggered Cell Death in MG63 Human Osteosarcoma Cells

Chien

Chou²,

Liang³

et al. 2014

Chin. J. Physiol.

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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 Ca²⁺ concentrations ([Ca²⁺]i) and viability in MG63 human osteosarcoma cells was explored. The Ca²⁺-sensitive fluorescent dye fura-2 was applied to measure [Ca²⁺]i. NPC-14686 at concentrations of 100-500 μM induced a [Ca²⁺]i rise in a concentration-dependent manner. The response was reduced by 80% by removing Ca²⁺. NPC-14686 induced Mn²⁺ influx leading to quenching of fura-2 fluorescence. NPC-14686-evoked Ca²⁺ entry was suppressed by nifedipine, econazole, SK&F96365, and protein kinase C inhibitor. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca²⁺]i rise. At 20-50 μM, NPC-14686 decreased cell viability, which was not reversed by chelating cytosolic Ca²⁺ 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 [Ca²⁺]i rise by inducing phospholipase C-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via protein kinase C-sensitive store-operated Ca²⁺ channels. NPC-14686 induced cell death that might involve apoptosis via mitochondrial pathways.

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