Ghosh J, Myers C E
University of Virginia Cancer Center, Charlottesville 22908, USA.
Biochem Biophys Res Commun. 1997 Jun 18;235(2):418-23. doi: 10.1006/bbrc.1997.6799.
Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a member of the omega-6 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.
花生四烯酸（5,8,11,14-二十碳四烯酸）是ω-6多不饱和脂肪酸家族的一员，发现在微摩尔浓度下它是体外人前列腺癌细胞生长的有效刺激物。对花生四烯酸不同代谢途径的选择性阻断（例如用布洛芬抑制环氧化酶、用SKF-525A抑制细胞色素P-450、用黄芩苷和BHPP抑制12-脂氧合酶、用AA861和MK886抑制5-脂氧合酶等）表明，花生四烯酸的生长刺激作用被5-脂氧合酶特异性抑制剂AA861和MK886抑制，但不被其他抑制剂抑制。添加5-脂氧合酶的二十碳四烯酸产物（5-羟基二十碳四烯酸）显示出对前列腺癌细胞生长的刺激作用，类似于花生四烯酸的刺激作用，而白三烯则无效。此外，5系列的二十碳四烯酸可以逆转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-羟基二十碳四烯酸的产生显著增加，而MK886可有效阻断这种增加。这些实验观察结果表明，花生四烯酸需要通过5-脂氧合酶途径进行代谢，以产生5-羟基二十碳四烯酸系列的二十碳四烯酸，从而对人前列腺癌细胞产生生长刺激作用。
