Dioscin suppresses the viability of ovarian cancer cells by regulating the VEGFR2 and PI3K/AKT/MAPK signaling pathways

Abstract

Diosgenin is a natural steroidal saponin that is extracted from a range of sources, including from fenugreek. It is a critical raw material in the synthesis of steroid hormone drugs, exhibiting antitumor, anti-inflammatory, antioxidation and a number of other significant pharmacological actions, possessing high pharmaceutical value. The aim of the present study was to investigate the effects of dioscin suppression on ovarian cancer cell growth and the mechanism of apoptosis induction by dioscin in ovarian cancer cells. The results of the present study demonstrated that dioscin decreased viability and induced apoptosis in SKOV3 human ovarian cancer cells in a dose-dependent manner. Dioscin significantly increased caspase-3 and caspase-9 activity, and increased the protein expression of Bax and cleaved poly(ADP-ribose) polymerase in SKOV3 cells. In addition, dioscin significantly suppressed vascular endothelial growth factor receptor (VEGFR)2, phosphoinositide 3-kinase (PI3K), phosphorylated AKT and phosphorylated p38 mitogen-activated protein kinase (MAPK) protein expression in SKOV3 cells. Taken together, to the best of our knowledge, the present study demonstrated for the first time that dioscin suppresses cell viability in ovarian cancer cells by regulating the VEGFR2 and PI3K/AKT/MAPK signaling pathways.

Saponins as cytotoxic agents: an update (2010–2018). Part I—steroidal saponins

“…Dioscin treatment increased cellular apoptosis in ovarian cancer SK-OV-3 cells in a dose-dependent manner. At the concentrations of 2.5 or 5 lM it significantly decreased PI3K and phosphorylated (p)-AKT, VEGFR2 protein expression compared with the non-treated control group, and induced expression of p-p38 protein (Guo and Ding 2018). Dioscin induced apoptosis in SGC-7901 cells in a dose-dependent manner (Hu et al 2011).…”

Recent Advances in the Pharmacological Activities of Dioscin

“…Dioscin could suppress the VEGF-induced blood vessel formation and downregulate VEGFR2 and its downstream protein kinases phosphoinositide 3-kinase (PI3K), Src, FAK, AKT, phosphorylated p38 mitogen-activated protein kinase (MAPK), and Erk1/2 expression. Phosphorylated P38 MAPK was upregulated in the human umbilical vein endothelial cells (HUVECs) [65] but decreased in ovarian cancer SKOV3 cells [66], the difference may be related to the different cell types. The in vivo studies also confirmed that dioscin could attenuate invasion and migration, decrease tumor size, and extend the lifespan of rats [53, 54].…”

Development of an Oriental Medicine Discrimination Method through Analysis of Steroidal Saponins in Dioscorea nipponica Makino and Their Anti-Osteosarcoma Effects

“…Interestingly, 4 showed the most potent anticancer effect, and the other compounds were less effective than 4 . Dioscin ( 4 ) has already been shown to inhibit the growth of colon, ovarian, and lung cancer and to be effective in apoptosis of cancer cells [41,42,43]. The anticancer effect caused by 4 examines whether the anticancer effect of osteosarcoma also uses the mitochondria signal pathway.…”