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Int. J. Mol. Sci. 2013, 14(10), 20139-20156; doi:10.3390/ijms141020139
Article

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

1,2
, 3
 and 4,5,*
Received: 1 July 2013; in revised form: 26 September 2013 / Accepted: 26 September 2013 / Published: 9 October 2013
(This article belongs to the collection Programmed Cell Death and Apoptosis)
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Abstract: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA Style

Huang F-J, Hsuuw Y-D, Chan W-H. Characterization of Apoptosis Induced by Emodin and Related Regulatory Mechanisms in Human Neuroblastoma Cells. International Journal of Molecular Sciences. 2013; 14(10):20139-20156.

Chicago/Turabian Style

Huang, Fu-Jen; Hsuuw, Yan-Der; Chan, Wen-Hsiung. 2013. "Characterization of Apoptosis Induced by Emodin and Related Regulatory Mechanisms in Human Neuroblastoma Cells." Int. J. Mol. Sci. 14, no. 10: 20139-20156.


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