Harmine suppresses the proliferation and migration of human ovarian cancer cells through inhibiting ERK/CREB pathway

Abstract

Ovarian cancer is the most lethal gynaecological cancer and the sixth most common cause of cancer related death among Western women. Recent studies show that harmine, a small-molecular β-carboline alkaloid present in medicinal plants, displayed obvious anticancer effects in several cancer cells. However, the effect of harmine on ovarian cancer is not well understood. In the present study, the effect of harmine on the cell proliferation and migration of ovarian cancer SKOV-3 cells and the underlying mechanism were investigated. Our results indicated that harmine significantly suppressed the proliferation of SKOV-3 cells in a dose-dependent manner. Interestingly, it also inhibited the epidermal growth factor (EGF)-induced proliferation of SKOV-3 cells. Moreover, the migration of SKOV-3 cells was markedly inhibited by harmine treatment. Further study showed that harmine inhibited not only the basal phosphorylation level of extra-cellular signal-regulated kinase1/2 (ERK1/2) and cyclic adenosine monophosphate response element-binding protein (CREB) but also EGF-induced ERK1/2 and CREB phosphorylation. Finally, harmine significantly suppressed the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) family MMP-2, and MMP-9. In conclusion, our data revealed that harmine inhibited the proliferation and migration of SKOV-3 cells, which might be mediated by ERK/CREB pathway. These findings elucidate that harmine may act as a potential therapeutic drug for ovarian cancer treatment.