Haraldsdóttir Sigurdís, Guolaugsdóttir Erna, Ingólfsdóttir Kristín, Ogmundsdóttir Helga M
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavík, Iceland.
Planta Med. 2004 Nov;70(11):1098-100. doi: 10.1055/s-2004-832657.
Lipoxygenases (LOXs) have been implicated in carcinogenesis in various cancer types. In the current study, three structurally different lichen metabolites, protolichesterinic acid (1), lobaric acid (2) and baeomycesic acid (3) were tested for anti-proliferative effects against 12 different human cancer cell lines. All compounds have known in vitro 5-LOX inhibitory activity, and 1 and 2 also inhibit 12-LOX. The activity of the lichen metabolites was compared to that of a specific 5-LOX inhibitor, zileuton (4). The following cancer cell lines were tested: Capan-1, Capan-2 and PANC-1 (all from pancreas), T47-D (breast), PC-3 (prostate), NCI-H1417 (small cell lung), NIH:OVCAR-3 (ovary), AGS (stomach), WiDr (colorectal), HL-60, K-562 and JURKAT (acute promyelocytic, erythro- and T-cell leukemia, respectively). Compound 1 showed the greatest inhibitory effect against all cell lines, with EC50 ranging from 2.4-18.1 microg mL(-1) (7.4-55.8 microM), followed by 2, with EC50 of 15.2 - 65.5 microg mL(-1) (33.2-143.6 microM). The effects of 3 and 4 were of similar orders of magnitude, with EC50 of 28.7 - >80 microg mL(-1) (76.8 - > 213.9 microM) and 12.9 - > 80 microg mL(-1) (50.4 - > 313.7 microM). The dual 5- and 12-LOX inhibitors 1 and to some extent 2 thus exert significant anti-proliferative effects against a variety of human cancer cell lines, while the selective 5-LOX inhibitors 3 and 4 are considerably less active.
脂氧合酶（LOXs）与多种癌症类型的致癌作用有关。在本研究中，测试了三种结构不同的地衣代谢产物，原地衣硬脂酸（1）、大叶地衣酸（2）和浅黄盘衣酸（3）对12种不同人类癌细胞系的抗增殖作用。所有化合物均具有已知的体外5-LOX抑制活性，且1和2还能抑制12-LOX。将地衣代谢产物的活性与特定的5-LOX抑制剂齐留通（4）的活性进行了比较。测试了以下癌细胞系：Capan-1、Capan-2和PANC-1（均来自胰腺）、T47-D（乳腺）、PC-3（前列腺）、NCI-H1417（小细胞肺癌）、NIH:OVCAR-3（卵巢）、AGS（胃）、WiDr（结肠直肠）、HL-60、K-562和JURKAT（分别为急性早幼粒细胞白血病、红白血病和T细胞白血病）。化合物1对所有细胞系显示出最大的抑制作用，EC50范围为2.4 - 18.1微克/毫升（7.4 - 55.8微摩尔），其次是2，EC50为15.2 - 65.5微克/毫升（33.2 - 143.6微摩尔）。3和4的作用强度相似，EC50分别为28.7 - >80微克/毫升（76.8 - >213.9微摩尔）和12.9 - >80微克/毫升（50.4 - >313.7微摩尔）。因此，双重5-和12-LOX抑制剂1以及在一定程度上的2对多种人类癌细胞系具有显著的抗增殖作用，而选择性5-LOX抑制剂3和4的活性则低得多。
