LIMK1 and LIMK2 regulate the actin cytoskeleton by phosphorylating and inactivating the cofilin family of actin-depolymerizing factors; LIMK1 also acts to destabilize microtubules and regulates cell motility, including tumor metastasis. The initial lead compound BMS-3 is a potent inhibitor of both LIMK activity and tubulin polymerization. In A549 cells, BMS-3 caused a dose-dependent reduction in cell count and induced mitotic arrest as shown by increases in total nuclear DNA intensity and histone H3 phosphorylation after 24 h treatment. The Affymetrix array contains probesets for 17 tubulin subunits; a dose-related decrease in signal for up to eight of these was seen with the treatment of BMS-3 suggesting it reduced the levels of tubulin transcripts. Relative to the vehicle control, addition of 10 μmol/L BMS-3 also decreased the rate and level of microtubule polymerization [2]. Inhibition of LIMK1 by BMS-3 resulted in lower levels of actin polymerization during capacitation and a dramatic decrease in the percentage of sperm that undergo acrosomal exocytosis [1].
BMS-3 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse sperm
1 or 50 μM
60 min
Inhibition of pLIMK1 resulted in significantly lower levels of F-actin polymerization
Dev Biol. 2015 Sep 15;405(2):237-49
trophoblast cells
2.5 µM, 5 µM, 10 µM
6 h
Inhibition of endogenous LIMK2 in differentiated trophoblast cells, results showed that BMS-3 treatment reduced the levels of pLIMK2Thr505 and pCOFILINSer3, and decreased the expression of trophoblast giant cell marker Prl2c2.
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