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Molecules 2017, 22(8), 1272; doi:10.3390/molecules22081272

Artesunate Activates the Intrinsic Apoptosis of HCT116 Cells through the Suppression of Fatty Acid Synthesis and the NF-κB Pathway

1
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China
2
Department of Biological Science, National University of Singapore, Singapore 117543, Singapore
3
Changzhou High-Tech Research Institute of Nanjing University, Institute of Biotechnology, Jiangsu Industrial Technology Research Institute and Jiangsu TargetPharma Laboratories Inc., Changzhou 213164, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 4 July 2017 / Revised: 27 July 2017 / Accepted: 27 July 2017 / Published: 8 August 2017
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
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Abstract

The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. Through Ingenuity Pathway Analysis, we discovered that the top-ranked ART-regulated biological pathways are abrogation of fatty acid biosynthetic pathway and mitochondrial dysfunction. Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. In addition, ART also regulates several proteins that are involved in NF-κB pathway, and our subsequent assays showed that ART suppresses the NF-κB pathway. These proteomic findings will contribute to improving our understanding of the underlying molecular mechanisms of ART for its therapeutic cytotoxic effect towards cancer cells. View Full-Text
Keywords: artesunate; fatty acid biosynthesis; HCT116; mitochondrial apoptosis; NF-κB pathway; proteomic analysis artesunate; fatty acid biosynthesis; HCT116; mitochondrial apoptosis; NF-κB pathway; proteomic analysis
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Chen, X.; Wong, Y.K.; Lim, T.K.; Lim, W.H.; Lin, Q.; Wang, J.; Hua, Z. Artesunate Activates the Intrinsic Apoptosis of HCT116 Cells through the Suppression of Fatty Acid Synthesis and the NF-κB Pathway. Molecules 2017, 22, 1272.

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