Curcolonol suppresses the motility of breast cancer cells by inhibiting LIM kinase�1 to downregulate cofilin 1 phosphorylation

Abstract

Curcolonol (CCL) is a furan type sesquiterpene isolated from several medical herbs. Based on previous results of anti-migratory activity screening, in this study, we investigated the effects of CCL on cancer cell motility. By invitro migration assay, we found that CCL significantly inhibited the vertical and horizontal migration of breast cancer cells induced by transforming growth factor (TGF)-β1. In addition, CCL also exerted inhibitory effects on F-actin polymerization in breast cancer cells when the cells were dyed with phalloidin. Given the close association between F-actin and ADF/cofilin, the effects of CCL on the expression and phosphorylation of cofilin1 were explored. It was observed that there were minimal changes in the expression of cofilin1; however, the phosphorylation of cofilin1 was significantly inhibited by CCL in a dose-dependent manner. Furthermore, CCL significantly inhibited the activity of LIM kinase1(LIMK1), although almost no effects were observed on LIMK1 expression and phosphorylation. However, the inhibitory effects of CCL on LIMK1 activity were antagonized and enhanced by the overexpression and knockdown of LIMK1, respectively. Based on the current data, it is thus suggested that the suppressive effects of CCL on breast cancer cell motility are due to its potential to reduce the phosphorylation of cofilin1, which may be associated with the inhibition of the catalytic activity of LIMK1.