Nordihydroguaiaretic acid-induced Ca2+ handling and cytotoxicity in human prostate cancer cells
Nordihydroguaiaretic acid-induced Ca2+ handling and cytotoxicity in human prostate cancer cells
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DOI：
10.1016/j.lfs.2004.04.043
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发表时间：
2004-09-24
期刊：
影响因子：
6.1
通讯作者：
Jan, CR
中科院分区：
文献类型：
--
作者：
Huang, JK;Chen, WC;Jan, CR
研究了去甲二氢愈创木酸（NDGA）（一种常用作脂氧合酶抑制剂的化合物）对PC 3人前列腺癌细胞中细胞内游离Ca 2+水平（[Ca 2 +]（i））的影响。[Ca2+]（i）通过使用Ca 2+敏感染料fura-2测量。NDGA以浓度依赖性方式增加[Ca 2 +]（i），EC 50为30 μ M。Ca 2+信号包括逐渐和持续的增加。去除细胞外Ca ~（2+）可部分降低NDGA诱导的[Ca ~（2+）]（i）增加，表明Ca ~（2+）信号是细胞外Ca ~（2+）内流和细胞内Ca ~（2+）释放共同作用的结果。NDGA诱导的Ca 2+内流通过测量NDGA诱导的Mn 2+偶联的Fura-2荧光猝灭而独立地证实。L-型钙通道阻断剂不影响NDGA诱导的Ca 2+内流。在无Ca 2+培养基中，用1 μ M毒胡萝卜素（一种内质网Ca（2+）泵抑制剂）预处理可以消除NDGA诱导的[Ca 2 +]（i）增加，相反，用NDGA预处理可以消除毒胡萝卜素诱导的[Ca 2 +]（i）增加。NDGA诱导的细胞内Ca ~（2+）释放不受磷脂酶C的抑制。用20-50 μ M NDGA过夜处理以浓度依赖性方式抑制细胞增殖速率。其他几种脂氧合酶抑制剂不改变[Ca 2 +]（i）。总的来说，这项研究表明，在前列腺细胞中，NDGA诱导[Ca 2 +]（i）增加，通过释放储存的Ca 2+从内质网的方式独立于磷脂酶C的活性，并通过引起Ca 2+内流。NDGA在较高浓度下也引起细胞毒性。(C)2004年由Elsevier Inc.出版
The effect of nordihydroguaiaretic acid (NDGA), a compound commonly used as a lipoxygenases inhibitor, on intracellular free Ca2+ levels ([Ca2+](i)) in PC3 human prostate cancer cells was investigated. [Ca2+](i) was measured by using the Ca2+-sensitive dye fura-2. NDGA increased [Ca2+](i) in a concentration-dependent manner with an EC50 of 30 muM. The Ca2+ signal comprised a gradual and sustained increase. Removal of extracellular Ca2+ partly decreased the NDGA-induced [Ca2+](i) increase, suggesting that the Ca2+ signal was due to both extracellular Ca2+ influx and intracellular Ca2+ release. NDGA-induced Ca2+ influx was independently confirmed by measuring NDGA-induced Mn2+-coupled quench of fura-2 fluorescence. The NDGA-induced Ca2+ influx was not affected by L-type Ca2+ channel blockers. In Ca2+-free medium, the NDGA-induced [Ca2+](i) increase was abolished by pretreatment with 1 muM thapsigargin (an endoplasmic reticulum Ca(2+)pump inhibitor), and conversely, pretreatment with NDGA abolished thapsigargin-induced [Ca2+](i) increase. NDGA-induced intracellular Ca2+ release was not altered by inhibition of phospholipase C. Overnight treatment with 20-50 muM NDGA inhibited cell proliferation rate in a concentration-dependent manner. Several other lipoxygenases inhibitors did not alter [Ca2+](i). Collectively, this study shows that in prostate cells, NDGA induced a [Ca2+](i) increase via releasing stored Ca2+ from the endoplasmic reticulum in a manner independent of phospholipase C activity, and by causing Ca2+ influx. NDGA also caused cytotoxicity at higher concentrations. (C) 2004 Published by Elsevier Inc.