Luteolin inhibits ER-α expression through ILK inhibition is regulated by a pathway involving Twist and YB-1

Increasing evidence supports the anti-estrogenic and/or anti-proliferative properties of luteolin, which is a natural flavonoid existing in herbs, vegetables and fruits. However, the molecular mechanisms responsible for these effects are only partially explored. In the present study, estrogen receptor-alpha (ER-α) was identified as a potential molecular target for luteolin. Our data indicated that treatment with luteolin engendered suppression of ER-α protein and mRNA expression in ER-α-positive breast cancer cells. Y-box binding protein-1 (YB-1) is a known transcriptional regulator of ER-α expression. In this studies it was demonstrated that luteolin decreased YB-1 protein and mRNA expression. Integrin-linked kinase (ILK) is able to phosphorylate many downstream effectors that have the potential to regulate YB-1 transcription. We provided evidence for a mechanism by which luteolin suppressed YB-1 expression through the downregulation of ILK/Akt/STAT3-regulated Twist expression in ER-α-positive breast cancer cells. Our data also showed that luteolin inhibited cancer migration and invasion through the inhibition of epithelial-mesenchymal transition (EMT). Taken together, these data indicate that the antitumorigenic effects of luteolin in ER-α-positive breast cancer cells may arise from its ability to reduce ER-α expression.