Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo

Abstract

Lung cancer is the leading cause of cancer‐related deaths. LIM domain kinase (LIMK) 1 is a member of serine/threonine kinase family and highly expressed in various cancers. Luteolin, a polyphenolic plant flavonoid, has been reported to suppress tumour proliferation through inducing apoptosis and autophagy via MAPK activation in glioma. However, the mechanism of luteolin on suppressing lung cancer growth is still unclear. We found that luteolin targeted LIMK1 from the in silico screening and significantly inhibited the LIMK1 kinase activity, which was confirmed with pull‐down binding assay and computational docking models. Treatment with luteolin inhibited lung cancer cells anchorage‐independent colony growth and induced apoptosis and cell cycle arrest at G1 phase. Luteolin also decreased the expression of cyclin D1 and increased the levels of cleaved caspase‐3 by down‐regulating LIMK1 signalling related targets, including p‐LIMK and p‐cofilin. Furthermore, luteolin suppressed the lung cancer patient‐derived xenograft tumour growth by decreasing Ki‐67, p‐LIMK and p‐cofilin expression in vivo. Taken together, these results provide insight into the mechanism that underlies the anticancer effects of luteolin on lung cancer, which involved in down‐regulation of LIMK1 and its interaction with cofilin. It also provides valuable evidence for translation towards lung cancer clinical trials with luteolin.