Bessadóttir M, Eiríksson F F, Becker S, Ögmundsdóttir M H, Ómarsdóttir S, Thorsteinsdóttir M, Ögmundsdóttir H M
Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland; Faculty of Pharmaceutical Sciences, University of Iceland, 101 Reykjavik, Iceland.
Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
Prostaglandins Leukot Essent Fatty Acids. 2015 Jul;98:39-47. doi: 10.1016/j.plefa.2015.04.009. Epub 2015 Apr 29.
Lipoxygenases (LOXs) and their products are involved in several biological functions and have been associated with carcinogenesis. Protolichesterinic acid (PA), a lichen metabolite, inhibits 5- and 12-LOX and has anti-proliferative effects on various cancer cell lines. Here, PA was shown to inhibit proliferation of multiple myeloma cells, RPMI 8226 and U266, and pancreatic cancer cells AsPC-1. Apoptosis was induced only in multiple myeloma cells. Cell-cycle associated changes in expression and sub-cellular localization of 5- and 12-LOX were not affected by PA but increased cytoplasmic localisation was found to accompany morphological changes at later stages. Assessment by mass spectrometry showed that PA entered the pancreatic cancer cells. However, effects on LOX metabolites were only evident after treatment with concentrations exceeding those having anti-proliferative effects and no effects were measurable in the myeloma cells. We conclude that the anti-proliferative and pro-apoptotic effects of PA are not mediated directly through inhibition of LOX activity.
脂氧合酶（LOXs）及其产物参与多种生物学功能，并与癌症发生相关。原地衣硬酸（PA）是一种地衣代谢产物，可抑制5-脂氧合酶和12-脂氧合酶，并对多种癌细胞系具有抗增殖作用。在此，PA被证明可抑制多发性骨髓瘤细胞RPMI 8226和U266以及胰腺癌细胞AsPC-1的增殖。仅在多发性骨髓瘤细胞中诱导了凋亡。5-脂氧合酶和12-脂氧合酶的表达及亚细胞定位的细胞周期相关变化不受PA影响，但在后期发现随着形态学变化，细胞质定位增加。质谱分析表明PA进入了胰腺癌细胞。然而，仅在使用超过具有抗增殖作用浓度的PA处理后，对LOX代谢产物的影响才明显，而在骨髓瘤细胞中未检测到影响。我们得出结论，PA的抗增殖和促凋亡作用并非直接通过抑制LOX活性介导。
