A biochemical study of cancer cell growth inhibitors from marine cyanobacteria

海洋蓝藻癌细胞生长抑制剂的生化研究

• 批准号: 21710237
• 负责人: TERUYA Toshiaki
• 金额: $ 2.91万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21710237/
• 关键词: シアノバクテリア; ビセリングビアサイド; ビセブロモアミド; プロテインキナーゼ阻害; Bisebromoamide; 細胞増殖阻害活性; Hela S_3腫瘍細胞; 新規鎖状ペプチド; Biselyngbyaside; 異常アミノ酸; 鎖状ペプチド; プロテインキナーゼ阻害活性; マクロリド配糖体; HeLa S_3腫瘍細胞; シアノバクテリア; ビセリングビアサイド; ビセブロモアミド; プロテインキナーゼ阻害; Bisebromoamide; 細胞増殖阻害活性; Hela S_3腫瘍細胞; 新規鎖状ペプチド; Biselyngbyaside; 異常アミノ酸; 鎖状ペプチド; プロテインキナーゼ阻害活性; マクロリド配糖体; HeLa S_3腫瘍細胞

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.

在我们正在进行的努力中，我们将新型的海洋蓝细菌代谢产物具有抗肿瘤活性，我们发现了双塞溴酰胺和双苯乙烯。双谢伯氨酰胺暴露的有效蛋白激酶抑制：通过PDGF（血小板来源的生长因子）在NRK细胞中ERK（细胞外信号调节的蛋白激酶）的磷酸化通过10至0.1μmBiseBisebromoamide的处理选择性抑制。双塞溴酰胺对10-0.1μM时AKT，PKD，PLCγ1或S6核糖体蛋白的磷酸化没有影响。双苯甲酰暴露于IC_ <50>值为0.1μg/mL的HELA S_3细胞的细胞毒性，暴露于差异的细胞毒性：中枢神经系统癌症SNB-78（GI_ <50>0.036μm）和肺癌NCI H522（GI______________________ED2222222222岁）尤其是敏感性。双苯甲酰是比较的阴性，表明它可能通过一种新型机制抑制癌细胞的增殖。