Induction of Apoptosis and Inhibition of Cell Migration and Tube-Like Formation by Dihydroartemisinin in Murine Lymphatic Endothelial Cells
- 4 July 2007
- journal article
- Published by S. Karger AG in Pharmacology
- Vol. 80 (4), 207-218
- https://doi.org/10.1159/000104418
Abstract
Dihydroartemisinin (DHA) is a semisynthesized agent from the artemisinin first extracted from the Chinese plant Artemisia annua. Previous studies have shown that artemisinin derivates, apart from their antimalarial activity, possess antitumor, antiangiogenic, and anti-inflammatory effects. In the present investigation, DHA was found to have a potent ability in influencing lymphatic endothelial cells (LECs) behavior. Murine LECs were isolated from benign lymphangiomas induced by intraperitoneal injection of incomplete Freund's adjuvant and identified by indirect immunofluorescence assay and fluorescence-activated cell sorting analysis to examine the expression of the specific marker VEGFR-3/Flt-4. When LECs were treated with DHA at 10 microg/ml, the growth of LECs was inhibited, and LECs showed typical apoptotic morphological features, with a higher apoptotic rate as compared with the controls. DHA also exerted a significant inhibitory effect on migration and tube-like formation of LECs in a dose-dependent manner. Quantitative RT-PCR further showed that DHA remarkably downregulated the expression of antiapoptotic bcl-2 mRNA, but upregulated that of the proapoptotic gene bax mRNA. In addition, DHA could strongly attenuate the mRNA and protein levels of VEGFR-3/Flt-4. In summary, these findings indicate that DHA may be useful as a potential lymphangiogenesis inhibitor under induction of cell apoptosis, inhibition of the migration, and formation of tube-like structures in LECs.This publication has 36 references indexed in Scilit:
- The Antimalarial Artemisinin Synergizes with Antibiotics To Protect against Lethal LiveEscherichia coliChallenge by Decreasing Proinflammatory Cytokine ReleaseAntimicrobial Agents and Chemotherapy, 2006
- Targeting lymphangiogenesis to prevent tumour metastasisBritish Journal of Cancer, 2006
- Generation and characterization of a mouse lymphatic endothelial cell lineCell and tissue research, 2006
- Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivoCancer Research, 2005
- Inhibition of Lymphogenous Metastasis Using Adeno-Associated Virus-Mediated Gene Transfer of a Soluble VEGFR-3 Decoy ReceptorCancer Research, 2005
- Artesunate reduces chicken chorioallantoic membrane neovascularisation and exhibits antiangiogenic and apoptotic activity on human microvascular dermal endothelial cellCancer Letters, 2004
- Inhibitory Effects of Artesunate on Angiogenesis and on Expressions of Vascular Endothelial Growth Factor and VEGF Receptor KDR/flk-1Pharmacology, 2004
- Lymphatic Endothelial Tumors Induced by Intraperitoneal Injection of Incomplete Freund's AdjuvantExperimental Cell Research, 1999
- Mitochondria and ApoptosisScience, 1998
- Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrinCancer Letters, 1995