Dihydroartemisinin induces endothelial cell anoikis through the activation of the JNK signaling pathway

作者

Zhang, J;Guo, L;Zhou, X;Dong, FY;Li, LQ;Cheng, ZW;Xu, YH;Liang, JY;Xie, Q;Liu, J

作者单位

[Zhang, Jiao] Shandong Univ, Shandong Prov Hosp, Dept Infect Dis, Jinan 250021, Shandong, Peoples R China.;-;[Guo, Ling; Dong, Fengyun; Li, Liqun; Xie, Qi; Liu, Ju] Shandong Univ, Shandong Prov Qianfoshan Hosp, Med Res Ctr, 16766 Jingshi Rd, Jinan 250014, Shandong, Peoples R China.;-;[Zhou, Xia] Shandong Univ, Shandong Prov Qianfoshan Hosp, Dept Tradit Chinese Med, Jinan 250014, Shandong, Peoples R China.;-;[Cheng, Zuowang; Xu, Yinghua] Taishan Med Coll, Tai An 271021, Shandong, Peoples R China.;-;[Liang, Jiyong] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.

摘要

Angiogenesis is required for the growth and metastasis of solid tumors. The anti-malarial agent dihydroartemisinin (DHA) demonstrates potent anti-angiogenic activity, but the underlying molecular mechanisms are not yet fully understood. During the process of angiogenesis, endothelial cells migrating from existing capillaries may undergo programmed cell death after detaching from the extracellular matrix, a process that is defined as anchorage-dependent apoptosis or anoikis. In the present study, DHA-induced cell death was compared in human umbilical vein endothelial cells (HUVECs) cultured in suspension and attached to culture plates. In suspended HUVECs, the cell viability was decreased and apoptosis was increased with the treatment of 50 mu M DHA for 5 h, while the same treatment did not affect the attached HUVECs. In addition, 50 mu M DHA increased the phosphorylation of c-Jun N-terminal kinase (JNK) in suspended HUVECs, but not in attached HUVECs, for up to 5 h of treatment. The JNK inhibitor, SP600125, reversed DHA-induced cell death in suspended HUVECs, suggesting that the JNK pathway may mediate DHA-induced endothelial cell anoikis. The data from the present study indicates a novel mechanism for understanding the anti-angiogenic effects of DHA, which may be used as a component for chemotherapy.

关键词

FOCAL ADHESION KINASE; N-TERMINAL KINASE; TUMOR ANGIOGENESIS; APOPTOSIS; GROWTH; CANCER; JUN; ANTIMALARIAL; SUPPRESSION; INHIBITION

基本信息

所属机构:保健消化内

归属医师: 张娇

PMID：27602117

UT：000382211900041

刊名:ONCOLOGY LETTERS

年，卷(期):2016年12卷3期

页码：1896-1900

DOI：10.3892/ol.2016.4870

附件： pdf

收录: SCIE