Arachidonic acid stimulates prostate cancer cell growth: Critical role of 5-lipoxygenase
Arachidonic acid stimulates prostate cancer cell growth: Critical role of 5-lipoxygenase
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DOI：
10.1006/bbrc.1997.6799
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发表时间：
1997-06-18
影响因子：
3.1
通讯作者：
Myers, CE
中科院分区：
文献类型：
--
作者：
Ghosh, J;Myers, CE
花生四烯酸(5，8，11，14-二十碳四烯酸)是omega-g多不饱和脂肪酸中的一员，在微摩尔浓度下能有效地促进人前列腺癌细胞的体外生长，选择性阻断花生四烯酸的不同代谢途径(如环氧合酶的布洛芬、细胞色素P-450的SKF-525A、12-脂氧合酶的黄芩素和BHPP、5-脂氧合酶的AA861和MK886等)。结果表明，花生四烯酸的促生长作用可被5-脂氧合酶特异性抑制剂AA861和MK886所抑制，但不被其他化合物所抑制。加入5-脂氧合酶的二十碳四烯产物(5-HETES)对前列腺癌细胞生长的刺激作用与花生四烯酸相似，而加入白三烯则无效，且5系列二十碳四烯可逆转MK886的生长抑制作用。最后，用花生四烯酸喂养的前列腺癌细胞显示5-HETE的产生显著增加，而MK886有效地阻断了这种作用。这些实验观察表明，花生四烯酸需要通过5-脂氧合酶途径代谢产生5-HETE系列二十碳四烯类化合物，才能促进人前列腺癌细胞的生长。(C)1997年学术出版社。
Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a member of the omega-g poly-unsaturated fatty acids, was found to be an effective stimulator of human prostate cancer cell growth in vitro at micromolar concentrations, Selective blockade of the different metabolic pathways of arachidonic acid (e.g. ibuprofen for cyclooxygenase, SKF-525A for cytochrome P-450, baicalein and BHPP for 12-lipoxygenase, AA861 and MK886 for 5-lipoxygenase, etc.) revealed that the growth stimulatory effect of arachidonic acid is inhibited by the 5-lipoxygenase specific inhibitors, AA861 and MK886, but not by others. Addition of the eicosatetraenoid products of 5-lipoxygenase (5-HETEs) showed stimulation of prostate cancer cell growth similar to that of arachidonic acid, whereas the leukotrienes were ineffective, Moreover, the 5-series of eicosatetraenoids could reverse the growth inhibitory effect of MK886. Finally, prostate cancer cells fed with arachidonic acid showed a dramatic increase in the production of 5-HETEs which is effectively blocked by MK886. These experimental observations suggest that arachidonic acid needs to be metabolized through the 5-lipoxygenase pathway to produce 5-HETE series of eicosatetraenoids for its growth stimulatory effects on human prostate cancer cells. (C) 1997 Academic Press.