Luteolin reduces migration of human glioblastoma cell lines via inhibition of the p-IGF-1R/PI3K/AKT/mTOR signaling pathway

Oncol Lett. 2017 Sep;14(3):3545-3551. doi: 10.3892/ol.2017.6643. Epub 2017 Jul 21.


Luteolin (3',4',5,7-tetrahydroxyflavone) is a common dietary flavonoid, which has been demonstrated to exert anticancer effects in multiple cancer models. However, the detailed mechanisms underlying the inhibitory effect of luteolin on glioblastoma cell metastasis remain poorly understood. The present study assessed the effects of luteolin in the U251MG and U87MG human glioblastoma cell lines. Luteolin treatment significantly inhibited glioblastoma cell migration, and this effect was associated with downregulated matrix metalloproteinase (MMP)-2, MMP-9 and upregulated tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. In addition, luteolin also inhibited the epithelial-mesenchymal transition-associated phenotype. Furthermore, the phosphorylated insulin-like growth factor-1 receptor/phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin (p-IGF-1R/PI3K/AKT/mTOR) signaling pathway was demonstrated to participate in these processes. The results of the present study demonstrated that the flavonoid luteolin reduced the migration of glioblastoma cells by altering p-IGF-1R/PI3K/AKT/mTOR activation, and may have potential applications for chemoprevention in a clinical setting.

Keywords: epithelial-mesenchymal transition; glioblastoma; luteolin; migration; phosphorylated insulin-like growth factor-1 receptor/phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin.