Next Article in Journal
Microscale Diffusion Measurements and Simulation of a Scaffold with a Permeable Strut
Next Article in Special Issue
Synthetic Resveratrol Analogue, 3,3',4,4',5,5'-Hexahydroxy-trans-Stilbene, Accelerates Senescence in Peritoneal Mesothelium and Promotes Senescence-Dependent Growth of Gastrointestinal Cancers
Previous Article in Journal
Determination of Homoarginine, Arginine, NMMA, ADMA, and SDMA in Biological Samples by HPLC-ESI-Mass Spectrometry
Previous Article in Special Issue
Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats
Int. J. Mol. Sci. 2013, 14(10), 20139-20156; doi:10.3390/ijms141020139

Characterization of Apoptosis Induced by Emodin and Related Regulatory Mechanisms in Human Neuroblastoma Cells

1 Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan 2 Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan 3 Department of Life Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan 4 Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan 5 Institute of Biomedical Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan
* Author to whom correspondence should be addressed.
Received: 1 July 2013 / Revised: 26 September 2013 / Accepted: 26 September 2013 / Published: 9 October 2013
(This article belongs to the collection Programmed Cell Death and Apoptosis)
View Full-Text   |   Download PDF [1117 KB, uploaded 19 June 2014]   |   Browse Figures


Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Recent studies have shown that emodin can induce or prevent cell apoptosis, although the precise molecular mechanisms underlying these effects are unknown. Experiments from the current study revealed that emodin (10–20 μM) induces apoptotic processes in the human neuroblastoma cell line, IMR-32, but exerts no injury effects at treatment doses below 10 μM. Treatment with emodin at concentrations of 10–20 μM led to a direct increase in the reactive oxygen species (ROS) content in IMR-32 cells, along with significant elevation of cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and -3, and cell death. Pretreatment with nitric oxide (NO) scavengers suppressed the apoptotic biochemical changes induced by 20 μM emodin, and attenuated emodin-induced p53 and p21 expression involved in apoptotic signaling. Our results collectively indicate that emodin at concentrations of 10–20 μM triggers apoptosis of IMR-32 cells via a mechanism involving both ROS and NO. Based on the collective results, we propose a model for an emodin-triggered apoptotic signaling cascade that sequentially involves ROS, Ca2+, NO, p53, caspase-9 and caspase-3.
Keywords: emodin; apoptosis; oxidative stress; calcium; nitric oxide emodin; apoptosis; oxidative stress; calcium; nitric oxide
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
MDPI and ACS Style

Huang, F.-J.; Hsuuw, Y.-D.; Chan, W.-H. Characterization of Apoptosis Induced by Emodin and Related Regulatory Mechanisms in Human Neuroblastoma Cells. Int. J. Mol. Sci. 2013, 14, 20139-20156.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert