Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells

Dong,Fengyun; Han,Ju; Jing,Guoxian; Chen,Xiaocui; Yan,Suhua; Yue,Longtao; Cao,Zhiqun; Liu,Xiaochun; Ma,Guozhao; Liu,Ju

doi:10.3892/ol.2016.5223

Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells

Authors:
- Fengyun Dong
- Ju Han
- Guoxian Jing
- Xiaocui Chen
- Suhua Yan
- Longtao Yue
- Zhiqun Cao
- Xiaochun Liu
- Guozhao Ma
- Ju Liu
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Affiliations: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Department of Medicine, Hospital of Shandong Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Published online on: October 5, 2016 https://doi.org/10.3892/ol.2016.5223
Pages: 4699-4704

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Abstract

Artemisinin and its derivatives are well-known anti-malaria drugs and in the early stages of research for cancer treatment. Dihydroartemisinin (DHA), a more water‑soluble derivative of artemisinin, has demonstrated strong anti-angiogenic activity. The purpose of the present study was to investigate the underlying molecular mechanisms of the effect of DHA on angiogenesis. Human umbilical vein endothelial cells (HUVECs) treated with DHA were examined for apoptosis and activation of the c‑Jun N‑terminal kinase (JNK) signaling pathway, one of the major mitogen‑activated protein kinase cascades. It was observed that 20 µM DHA induces transient activation of JNK in HUVECs. DHA also elevates the expression of cyclooxygenase‑2 and matrix metalloproteinase‑13, which is abolished by treatment with the JNK inhibitor SP600125. Although DHA persistently increases inhibitor of κB‑α protein and thus inhibits nuclear factor‑κB signaling, it does not affect apoptosis or caspase 3/9 activities in HUVECs. The present study provides key information for understanding the effects of DHA on endothelial cells, which is required for investigating its potential for clinic application as a chemotherapeutic agent.

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