Violaceols Function as Actin Inhibitors Inducing Cell Shape Elongation in Fibroblast Cells
Violaceols Function as Actin Inhibitors Inducing Cell Shape Elongation in Fibroblast Cells
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DOI：
10.1271/bbb.120074
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发表时间：
2012-08-01
影响因子：
1.6
通讯作者：
Ahn, Jong Seog
中科院分区：
文献类型：
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作者：
Asami, Yukihiro;Jang, Jae-Hyuk;Ahn, Jong Seog
紫罗兰醇-I和-II分离自海洋来源的真菌代谢产物的分级文库。这些化合物增加了细胞内的钙离子浓度，并在3小时内引起大鼠成纤维细胞3 Y1细胞中的F-肌动蛋白聚集，导致细胞形状伸长。钙离子螯合剂BAPTA-AM（1，2-双（2-氨基苯氧基）乙烷-N，N，N '，N' -四乙酸四（乙酰氧基甲酯））可抑制3 Y1细胞中紫醇-I和紫醇-II诱导的F-肌动蛋白聚集，因此紫醇-I和紫醇-II以钙依赖方式起作用。Violaceol-I和-II在体外以剂量依赖性方式抑制G-肌动蛋白聚合，并与G-肌动蛋白密切相关，解离平衡常数分别为1.44 x 10（-8）M和2.52 x 10（-9）M。在这里，我们报告的一个新的功能的violaceol-I和-II作为肌动蛋白抑制剂的鉴定。Violaceol-I和-II通过3 Y1成纤维细胞中的F-肌动蛋白聚集诱导细胞形状伸长。这些化合物可能使研究人员对肌动蛋白在肿瘤发生中的作用有新的认识，并导致开发其他抗肿瘤药物。
Violaceol-I and -II were isolated from a fractionated library of marine-derived fungal metabolites. These compounds increased the calcium ion concentration inside the cell and caused F-actin aggregation in rat fibroblast 3Y1 cells within 3 h resulting in cell shape elongation. Calcium chelator BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N' -tetraacetic acid tetrakis (acetoxymethyl ester) inhibited violaceol-I and -II induced F-actin aggregation in 3Y1 cells, and hence violaceol-I and -II act in a calcium dependent manner. Violaceol-I and -II inhibited G-actin polymerization in vitro in a dose-dependent manner and strongly associated with G-actin, at dissociation equilibrium constants of 1.44 x 10(-8) M and 2.52 x 10(-9) M respectively. Here we report the identification of a novel function of violaceol-I and -II as actin inhibitors. Violaceol-I and -II induced cell shape elongation through F-actin aggregation in 3Y1 fibroblasts. These compounds may give researchers new insights into the role of actin in tumorigenesis and lead to the development of additional anti-tumor drugs.