Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells via PI3K/AKT and ERK 1/2 MAPK signal transduction

Abstract

Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical properties against various chronic diseases and types of cancer. However, little is known about its preventative effects on epithelial ovarian cancer, a disease that is associated with a low survival rate, a poor prognosis and a high rate of recurrence. The results of the present study demonstrated that the proliferation of SKOV3 cells decreased in a dose-dependent manner in response to treatment with delphinidin, and the phosphorylation of carcinogenic protein kinases associated with the progression of epithelial ovarian cancer was affected by delphinidin treatment. The levels of phosphorylated protein kinase B (AKT), ribosomal protein S6 kinase beta-1 (P70S6K), ribosomal protein S (S6), extracellular signal-regulated kinase (ERK)1/2 and p38 were suppressed by increasing concentrations of delphinidin. Furthermore, the combination of certain pharmacological inhibitors, including phosphoinositide 3-kinase (PI3K; LY294002), ERK1/2 (U0126) and delphinidin significantly reduced the proliferation of SKOV3 cells and the phosphorylation of each of those target proteins. In addition, delphinidin treatment exerted anti-proliferative effects on paclitaxel-resistant SKOV3 cells, compared with treatment with paclitaxel alone. These results indicate that delphinidin inhibits the proliferation of SKOV3 cells through inactivation of PI3K/AKT and ERK1/2 mitogen-activated protein kinase signaling cascades, and that this cell signaling pathway may be a pivotal therapeutic target for the prevention of epithelial ovarian cancer, including paclitaxel-resistant ovarian cancer.