TY - JOUR
T1 - Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells via PI3K/AKT and ERK 1/2 MAPK signal transduction
AU - Lim, Whasun
AU - Song, Gwonhwa
N1 - Funding Information:
The authors thank Dr Fuller W. Bazer (Texas A&M University, College Station, USA) for their thoughtful editing and comments on this manuscript. The present study was supported by grants from the Basic Science Research Program (grant no. 2015R1D1A1A01059331) of the Republic of Korea and also supported by School of Life Sciences and Biotechnology for BK21 PLUS, Korea University.
Publisher Copyright:
© 2017, Spandidos Publications. All rights reserved.
PY - 2017
Y1 - 2017
N2 - Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical proper-ties 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 recur-rence. 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 β-1 (P70S6K), ribosomal protein S (S6), extracellular signal-regulated kinase (ERK)1/2 and p38 were suppressed by increasing concentra-tions 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.
AB - Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical proper-ties 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 recur-rence. 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 β-1 (P70S6K), ribosomal protein S (S6), extracellular signal-regulated kinase (ERK)1/2 and p38 were suppressed by increasing concentra-tions 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.
KW - Cell proliferation
KW - Chemotherapy
KW - Delphinidin
KW - Ovarian cancer
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=85020167241&partnerID=8YFLogxK
U2 - 10.3892/ol.2017.6232
DO - 10.3892/ol.2017.6232
M3 - Article
AN - SCOPUS:85020167241
SN - 1792-1074
VL - 14
SP - 810
EP - 818
JO - Oncology Letters
JF - Oncology Letters
IS - 1
ER -