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Int. J. Mol. Sci. 2015, 16(8), 18956-18975; doi:10.3390/ijms160818956

A Natural Triterpene Derivative from Euphorbia kansui Inhibits Cell Proliferation and Induces Apoptosis against Rat Intestinal Epithelioid Cell Line in Vitro

1
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
2
Medicament Department, Zhangjiagang Hospital of Traditional Chinese Medicine, Suzhou 215600, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Masato Matsuoka
Received: 26 June 2015 / Revised: 1 August 2015 / Accepted: 4 August 2015 / Published: 12 August 2015
(This article belongs to the Section Molecular Toxicology)
View Full-Text   |   Download PDF [7308 KB, uploaded 12 August 2015]   |  

Abstract

Kansenone is a triterpene from the root of the traditional Chinese medicine, Euphorbia kansui. However, kansenone exerts serious toxicity, but the exact mechanism was not clear. In this work, the effects of kansenone on cell proliferation, cell cycle, cell damage, and cell apoptosis were investigated. The suppression of cell proliferation was assessed via the colorimetric MTT assay, and cell morphology was visualized via inverted microscopy after IEC-6 cells were incubated with different concentrations of kansenone. Reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) content were detected for evaluating cell damage. RNase/propidium iodide (PI) labeling for evaluation of cell cycle distribution was performed by flow cytometry analysis. Annexin V-fluorescein isothiocyanate (FITC)/PI and Hoechst 33342/Annexin V-FITC/PI staining assay for cell apoptosis detection were performed using confocal laser scanning microscopy and high content screening. Moreover, apoptosis induction was further confirmed by transmission electron microscope (TEM) and JC-1 mitochondrial membrane potential, western blot and RT-PCR analysis. The results demonstrated that kansenone exerted high cytotoxicity, induced cell arrest at G0/G1 phase, and caused mitochondria damage. In addition, kansenone could up-regulate the apoptotic proteins Bax, AIF, Apaf-1, cytochrome c, caspase-3, caspase-9, caspase-8, FasR, FasL, NF-κB, and TNFR1 mRNA expression levels, and down-regulate the anti-apoptotic Bcl-2 family proteins, revealing that kansenone induces apoptosis through both the death receptor and mitochondrial pathways. View Full-Text
Keywords: kansenone; cell proliferation; cell damage; cell cycle; cell apoptosis; death receptor pathway; mitochondrial pathway kansenone; cell proliferation; cell damage; cell cycle; cell apoptosis; death receptor pathway; mitochondrial pathway
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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. (CC BY 4.0).

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MDPI and ACS Style

Cheng, F.; Yang, Y.; Zhang, L.; Cao, Y.; Yao, W.; Tang, Y.; Ding, A. A Natural Triterpene Derivative from Euphorbia kansui Inhibits Cell Proliferation and Induces Apoptosis against Rat Intestinal Epithelioid Cell Line in Vitro. Int. J. Mol. Sci. 2015, 16, 18956-18975.

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