Inhibition of TPA‑induced metastatic potential by morin hydrate in MCF‑7 human breast cancer cells via the Akt/GSK‑3β/c‑Fos signaling pathway.

Abstract

Plant flavonoid 2',3,4',5,7‑pentahydroxyflavone (morin hydrate), isolated from the family Moraceae (MorusalbaL.), is known to have anti‑inflammatory and anticancer effects. However, its pharmaceutical effects on metastasis have not been fully elucidated to date. Therefore, the current study investigated the effects of morin hydrate on cancer metastasis in MCF‑7 human breast cancer cells. The results showed that morin hydrate suppressed 12‑O‑tetradecanoylphorbol‑13‑acetate(TPA)‑induced cell migration and invasion via the inhibition of matrix metalloproteinase(MMP)‑9 activity. Furthermore, gene expression level of MMP‑9, MMP‑7, urokinase plasminogen activator(uPA), uPA receptor (uPAR) and fibronectin were significantly decreased by morin hydrate treatment. Morin hydrate inhibited the phosphorylation of Akt and glycogen synthase kinase (GSK)‑3β, and downregulated the expression of an activator protein‑1 subunit c‑Fos. In addition, the GSK‑3β phosphorylation and c‑Fos expression were suppressed by PI3K/Akt pathway inhibitors, LY294002 and wortmannin. Taken together, these results demonstrated that morin hydrate reduced the metastatic potential in TPA‑treated MCF‑7 human breast cancer cells via the inhibition of MMPs, uPA and uPAR, and the underlying Akt/GSK‑3β/c‑Fos pathway. Therefore, the present investigation suggested that morin hydrate may be a natural substance with a preventive potential for metastasis in breast cancer cells.