α-Tomatine inactivates PI3K/Akt and ERK signaling pathways in human lung adenocarcinoma A549 cells: Effect on metastasis

This study first investigates the anti-metastastic effect of α-tomatine in the human lung adenocarcinoma cell line: A549. In this study, we first noted α-tomatine inhibited A549 cells invasion and migration by wound-healing assay and Boyden chamber assay. The data also showed α-tomatine could inhibit phosphorylation of Akt and extracellular signal-regulated kinase 1 and 2 (ERK1/2), which is involved in the up-regulating matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) or urokinase-type plasminogen activator (u-PA), whereas it did not affect phosphorylation of c-Jun N-terminal kinase (JNK) and p38. Next, α-tomatine significantly decreased the nuclear levels of nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Also, treating A549 cells with α-tomatine also leads to a dose-dependent inhibition on the binding abilities of NF-κB and activator protein-1 (AP-1). Further, the treatment of inhibitors specific for PI3K (Wortmannin) or ERK (U0126) to A549 cells could cause reduced activities of MMP-2, MMP-9, and u-PA. These results showed α-tomatine could inhibit the metastatic ability of A549 cells by reducing MMP-2, MMP-9, and u-PA activities through suppressing phosphoinositide 3-kinase/Akt (PI3K/Akt) or ERK1/2 signaling pathway and inhibition NF-κB or AP-1 binding activities. These findings proved α-tomatine might be an anti-metastastic agent against human lung adenocarcinoma.