title: 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.
authors.affiliation: Department of Biotechnology and Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Whasun
authors.initials: W
authors.lastname: Lim
authors.affiliation: Department of Biotechnology and Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Changwon
authors.initials: C
authors.lastname: Yang
authors.affiliation: Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.affiliation: Department of Biotechnology and Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. ghsong@korea.ac.kr.
authors.forename: Gwonhwa
authors.initials: G
authors.lastname: Song
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000201:enzymology* / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D042541:Intracellular Space / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D013997:Time Factors
chemical_list: D000880:Anthraquinones; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C027113:chrysophanic acid; D017239:Paclitaxel; D002945:Cisplatin