title: Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells.
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.
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Jing
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Yan
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Longtao
authors.initials: L
authors.lastname: Yue
authors.affiliation: Department of Medicine, Hospital of Shandong Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Guozhao
authors.initials: G
authors.lastname: Ma
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
keywords: angiogenesis; apoptosis; c-Jun N-terminal kinase signaling; dihydroartemisinin; endothelial cell