RA-VII, a cyclic depsipeptide, changes the conformational structure of actin to cause G2 arrest by the inhibition of cytokinesis.
In L1210 cells, RA-VII (0.1-100 nM) caused the concentration-dependent inhibition of the proliferation and G2 arrest. Treatment of PC12 cells with 10 nM RA-VII changed cell shape round with binucleation, suggesting the inhibition of cytokinesis. The fluorescence intensity of FITC-phalloidin bound to F-actin was enhanced by RA-VII. In surface plasmon resonance experiments, the signal of F-actin was modified by RA-VII in close agreement with a concentration of FITC-phalloidin binding to F-actin. These results suggest that RA-VII causes the conformational change of F-actin and the stabilization of actin filaments to induce G2 arrest.
Fujiwara
Hironori
H
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Saito
Shin-ya
SY
Hitotsuyanagi
Yukio
Y
Takeya
Koichi
K
Ohizumi
Yasushi
Y
D000199:Actins / Q000737:chemistry*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects*; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016716:PC12 Cells; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010590:Phalloidine / Q000031:analogs & derivatives / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects*; D051381:Rats; D020349:Surface Plasmon Resonance
D000199:Actins; D010456:Peptides, Cyclic; D010590:Phalloidine; C043548:RA VII