A biochemical study of cancer cell growth inhibitors from marine cyanobacteria

在我们正在进行的努力，以分离新的海洋蓝藻代谢产物与抗肿瘤活性，我们发现bisebromoamide和biselyngbyaside。双sebromoamide表现出强效的蛋白激酶抑制作用：10 - 0.1μM双sebromoamide处理可选择性抑制PDGF（血小板衍生生长因子）刺激的NRK细胞中ERK（细胞外信号调节蛋白激酶）的磷酸化。在10-0.1μM浓度下，双sebromoamide对AKT、PKD、PLCγ1或S6核糖体蛋白的磷酸化无影响。Biselynbyaside对HeLa S_3细胞有一定的杀伤作用，IC值<50>为0.1μg/mL，对中枢神经系统肿瘤SNB-78（GI_（<50>0.036）μM）和肺癌NCI H522（GI_（<50>0.067）μM）的杀伤作用差异显著。Biselyngbyaside是比较阴性的，表明它可能通过一种新的机制抑制癌细胞增殖。

In our ongoing efforts to isolate novel marine cyanobacterial metabolites with antitumor activity, we found bisebromoamide and biselyngbyaside. Bisebromoamide exhibited potent protein kinase inhibition: the phosphorylation of ERK (extracellular signal regulated protein kinase) in NRK cells by PDGF (platelet-derived growth factor)-stimulation was selectively inhibited by treatment with 10 to 0.1μM of bisebromoamide. Bisebromoamide had no effect on the phosphorylation of AKT, PKD, PLCγ1, or S6 ribosomal protein at 10-0.1μM. Biselyngbyaside exhibited cytotoxicity against HeLa S_3 cells with an IC_<50> value of 0.1μg/mL and exhibited differential cytotoxicities : the central nervous system cancer SNB-78 (GI_<50> 0.036μM) and lung cancer NCI H522 (GI_<50> 0.067μM) were especially sensitive. Biselyngbyaside was COMPARE-negative, indicating that it likely inhibits cancer cell proliferation through a novel mechanism.