alpha-Solanine Inhibits Human Melanoma Cell Migration and Invasion by Reducing Matrix Metalloproteinase-2/9 Activities

摘要

alpha-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of alpha-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of alpha-solanine on metastasis in vitro. Data demonstrated that alpha-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of alpha-solanine, cell migration and invasion were markedly suppressed. Furthermore, alpha-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that alpha-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, alpha-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-kappa B), suggesting that alpha-solanine inhibited NF-kappa B activity. Taken together, the results suggested that alpha-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-kappa B activity. These findings reveal new therapeutic potential for alpha-solanine in anti-metastatic therapy.