Chrysophanol is an anthraquinone compound, mainly isolated from rhubarb, with 
anti-cancer effects on some types of cancer cells. However, effects of 
chrysophanol on human choriocarcinoma cells are not known. Therefore, the 
objective of this study was to determine effects of chrysophanol on 
choriocarcinoma cells (JAR and JEG-3) and identify signal transduction cascades 
activated by chrysophanol. Results of present study, showed that chrysophanol 
decreased cell viability and induced apoptosis of JEG-3, but not JAR cells, in a 
dose-dependent manner. Chrysophanol also increased oxidative stress in JEG-3 
cells by inducing ROS generation followed by mitochondrial dysfunction including 
depolarization of mitochondrial inner membrane potential. Western blot analysis 
revealed that ERK1/2, P90RSK, AKT, and P70S6K were increased significantly in 
JEG-3 cells by chrysophanol. Next, we investigated chrysophanol-mediated effects 
on proliferation of JEG-3 cells using pharmacological inhibitors of PI3K/AKT 
(LY294002) and ERK1/2 (U0126). Inhibition of AKT and ERK1/2 prevented 
chrysophanol-induced stimulation of proliferation of JEG-3 cells. In addition, 
the phosphorylation of AKT and ERK1/2 was suppressed by LY294002 and U0126 in 
JEG-3 cells treated with chrysophanol, whereas, the AKT protein was activated by 
pre-treatment of JEG-3 cells with U0126. Furthermore, we compared therapeutic 
effects of chrysophanol with cisplatin and paclitaxel which are conventional 
salvage regimens for choriocarcinoma. Our results verified that chrysophanol has 
synergistic effects with traditional therapy to increase apoptosis of JEG-3 
cells. Collectively, these results indicate that chrysophanol is a potential 
effective chometherapeutic agent for treatment of choriocarcinoma therapy, and 
minimizing side effects of conventional treatment regimens. J. Cell. Physiol. 
232: 331-339, 2017. © 2016 Wiley Periodicals, Inc.