Chrysophanol Induces Apoptosis of Choriocarcinoma Through Regulation of ROS and the AKT and ERK1/2 Pathways

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.

Antitumor Effects of Chrysophanol in Malignant Optic Nerve Meningioma Cell Lines are Mediated via Caspase Activation, Induction of Mitochondrial Mediated Apoptosis, Mitochondrial Membrane Depolarization and Targeting the Mitogen-Activated Protein Kinase Signaling Pathway

“…These observations are also supported by previous studies where chrysophanol has been shown to trigger apoptosis of the breast cancer cells [16]. Chrysophanol has been shown to induce anticancer effects through the activation of the ROS machinery [12,13] and in this study, we found that chrysophanol increased the ROS levels and at the same time decreased the MMP levels. Mitogen-activated protein kinase signaling pathway is often activated in the cancer cells [17] and in this study, we found that chrysophanol could block this pathway in the CH157-MN cells suggestive of the potent anticancer effects…”

“…In yet another study, chrysophanol halted the ATP synthesis in liver cancer cells [12]. In choriocarcinoma cells, chrysophanol causes apoptosis via modulation of ROS [13]. These studies suggest that chrysophanol may prove a potent anticancerous molecule.…”

“…Previous studies have shown that chrysophanol inhibits the growth of cancer cells through different mechanisms [10]. It has been shown to trigger necrosis of the liver cancer cells by inducing the formation of ROS [10][11][12][13]. Similarly, in A549 lung cancer cells, chrysophanol causes the reduction of MMP loss to trigger cell death [11].…”

Chrysophanol induces cell death and inhibits invasiveness via mitochondrial calcium overload in ovarian cancer cells

“…[17][18][19] However, the mechanism of action of chrysophanol has not been elucidated for ovarian cancer. Previous studies demonstrated that chrysophanol triggers cell death in several cancer cell lines, including liver cancer, lung cancer, prostate cancer, and gestational choriocarcinoma, through the induction of mitochondrial dysfunction and oxidative stress.…”

Challenges and developments of self-assembled monolayers and polymer brushes as a green lubrication solution for tribological applications

“…13. 198,199 Reduced graphene oxide (RGO) sheets are prepared by heating GO sheets aer assembly. The modied Ti surfaces were then tested using a reciprocating pin on plate tribometer under dry conditions against a silicon nitride ball under 100 mN load and 1 Hz frequency.…”