A biochemical study of cancer cell growth inhibitors from marine cyanobacteria

在我们正在进行的分离具有抗肿瘤活性的新型海洋蓝藻代谢物的努力中，我们发现了双溴胺和双倍半乳糖苷。双溴胺具有较强的蛋白激酶抑制作用：10~0.1μM的双溴胺可选择性地抑制血小板衍生生长因子刺激的NRK细胞外信号调节蛋白激酶的磷酸化。双溴酰胺对γ1或S6核糖体蛋白的磷酸化在10-0.1μ时无明显影响，对HeLa S_3细胞有明显的细胞毒作用，IC_(50)为0.1μg/mL，对中枢神经系统癌SNB-78(GI_&lt；50&Gt；0.036μM)和肺癌NCI H522(GI&lt；50&GT；0.067μM)尤为敏感。Biselyngbyside是比较阴性的，表明它可能通过一种新的机制抑制癌细胞的增殖。

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.