Cellular Changes of Rat Embryonic Fibroblasts by an Actin-Polymerization Inhibitor, Bistheonellide A, from a Marine Sponge

Cell Structure and Function

Hideaki Karaki¹  Hiroshi Ozaki¹  Shugo Watabe³  Shun-ichi Wada³  Shigeki Matsunaga³  Nobuhiro Fusetani³  Shin-ya Saito² 

[1] Department of Veterinary Pharmacology, Graduate School of Agricultural and Life Sciences, The University of Tokyo;Department of Animal Sciences, Iwate University;Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo

关键词: actin;    electroporation;    cytoskeleton;    cell division;    cell mobility;    Dictyostelium;   

DOI  :  10.1247/csf.21.199

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(32)Cited-By(9)Bistheonellide A, an inhibitor of actin polymerization from the marine sponge Theonella sp., was introduced at a concentration of 100 nM into rat 3Y1 fibroblast of 2.4 × 104 cells/ml. Within 1 h, it disrupted stress fibers, accompanied by a marked change of the cell morphology, resulting in the formation of processes from the cell surface. Further incubation for 24 h in the presence of 100 nM bistheonellide A led to binucleation in most cells and subsequent inhibition of cell cycle progression. When bistheonellide A was withdrawn from the culture medium, binuclear cells began to grow again within 20 h and reverted to mononuclear morphology. Flow cytometric analysis by fluorescence-activated cell sorting showed that 2C diploid DNA content in G1 phase was changed into 4C content of tetraploid for the bistheonellide A treated-cells in G1 phase and into SC content during G2 and M phase. Therefore, we suggested that the bistheonellide A treatment inhibited cytokinesis, but not mitosis in M phase, and that treated cells were arrested at the early G1 phase. These effects of bistheonellide A on the cell cycle progression of 3Y1 fibroblast were also observed more prominently in cells synchronized in S phase with hydroxyurea. Cells in GO phase were then activated by the addition of fetal calf serum in the presence of 100 nM bistheonellide A. Cell cycle progression of the bistheonellide A-treated cells was obviously slowed down or completely inhibited during G1 phase. These results reveal that actin filaments are not only essential to cytokinesis but also for promoting the progression of cell cycle from G1 to S phase.

【 授权许可】

Unknown