Chrysophanol Induces Apoptosis of Choriocarcinoma Through Regulation of ROS and the AKT and ERK1/2 Pathways. Issue 2 (2nd June 2016)

• Record Type: Journal Article
• Authors: Lim, Whasun; Yang, Changwon; Bazer, Fuller W.; Song, Gwonhwa
• Is Part Of: Journal of cellular physiology. Volume 232:Issue 2(2017:Feb.)
• Page Start: 331
• Page End: 339
• Publication Date: 2016-06-02
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25423
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : 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. Abstract : Results of the present study indicated that chrysophanol has anti‐cancer effects by reducing cell viability and inducing apoptosis by increasing ROS production and decreasing mitochondrial membrane potential through the ERK1/2 and AKT signaling cascades. Moreover, chrysophanol is a potential effective chometherapeutic agent for treatment of choriocarcinoma therapy when combined with cisplatin and paclitaxel and minimizing side effects of conventional treatment regimens.