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首页> 外文期刊>Life sciences >NPC-14686 (Fmoc-l-homophenylalanine)-induced CaCa2+ increases and death in human prostate cancer cells.
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NPC-14686 (Fmoc-l-homophenylalanine)-induced CaCa2+ increases and death in human prostate cancer cells.

机译：NPC-14686（Fmoc-1-高苯丙氨酸）诱导的CaCa2 +增加并在人前列腺癌细胞中死亡。

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摘要

The effect of NPC-14686, a potential anti-inflammatory drug, on cytosolic free Ca2+ levels ([Ca2+]i) and growth in PC3 human prostate cancer cells was examined by using fura-2 as a fluorescent Ca2+ indicator and WST-1 as a fluorescent growth dye. NPC-14686 at concentrations above 10 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 100 microM. NPC-14686-induced Ca2+ influx was confirmed by Mn2+ quench of fura-2 fluorescence. The Ca2+ signal was also reduced by removing extracellular Ca2+. Pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+ nearly abolished 200 microM NPC-14686-induced Ca2+ release; and conversely pretreatment with NPC-14686 completely inhibited thapsigargin-induced Ca2+ release. The Ca2+ release induced by 200 microM NPC-14686 was not affected by inhibiting phospholipase C with 2 microM U73122. Overnight treatment with 1-500 microM NPC-14686 decreased cell viability in a concentration-dependent manner. These findings suggest that in human PC3 prostate cancer cells, NPC-14686 increases [Ca2+]i by evoking extracellular Ca2+ influx and releasing intracellular Ca2+ from the endoplasmic reticulum via a phospholiase C-independent manner. NPC-14686 may be cytotoxic to prostate cancer cells.
机译：NPC-14686，一种潜在的抗炎药，对呋喃2作为荧光Ca 2+指示剂和WST-1作为对PC3人前列腺癌细胞中胞质游离Ca 2+水平（[Ca 2+] i）和生长的影响。荧光生长染料。浓度高于10 microM的NPC-14686以浓度依赖的方式增加[Ca2 +] i，EC50值为100 microM。 NPC-14686诱导的Ca2 +内流通过fura-2荧光的Mn2 +猝灭来确认。通过去除细胞外Ca 2+，也减少了Ca 2+信号。用1 microM thapsigargin（内质网Ca2 +泵抑制剂）预处理以耗尽内质网Ca2 +几乎消除了200 microM NPC-14686诱导的Ca2 +释放;相反，用NPC-14686预处理则完全抑制了毒胡萝卜素诱导的Ca2 +释放。 200 microM NPC-14686诱导的Ca2 +释放不受2 microM U73122抑制磷脂酶C的影响。用1-500 microM NPC-14686隔夜处理会以浓度依赖性方式降低细胞活力。这些发现表明，在人PC3前列腺癌细胞中，NPC-14686通过引起细胞外Ca2 +内流并通过非磷酸化酶C独立方式从内质网释放细胞内Ca2 +来增加[Ca2 +] i。 NPC-14686可能对前列腺癌细胞有细胞毒性。

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