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

Whasun Lim, Changwon Yang, Fuller W. Bazer, Gwonhwa Song

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 2016

Fingerprint

Choriocarcinoma
MAP Kinase Signaling System
Apoptosis
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
chrysophanic acid
Cells
Rheum
70-kDa Ribosomal Protein S6 Kinases
Salvaging
Anthraquinones
Signal transduction
Phosphorylation
Oxidative stress
Mitochondrial Membrane Potential
Depolarization
Therapeutic Uses
Paclitaxel
Phosphatidylinositol 3-Kinases
Cisplatin
Signal Transduction

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Chrysophanol Induces Apoptosis of Choriocarcinoma Through Regulation of ROS and the AKT and ERK1/2 Pathways. / Lim, Whasun; Yang, Changwon; Bazer, Fuller W.; Song, Gwonhwa.

In: Journal of Cellular Physiology, 2016.

Research output: Contribution to journalArticle

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