Dihydroartemisinin suppresses cell proliferation, invasion, and angiogenesis in human glioma U87 cells

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, which is a well tolerated and effective drug for malaria treatment, has shown potent antitumor ability. This study is explored to evaluate whether DHA can inhibit glioma cell proliferation, invasion, and glioma cell mediated angiogenesis. We determined the glioma U87 cell proliferation by Cell Counting Kit-8 (CCK-8) assay, fluorescence, and flow cytometry (FCM). The invasion and migration of U87 cell were tested by wound-scratch assay and martrigel-transwell methods, while its angiogenesis tube formation assay was tested with reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Our data suggested that DHA inhibited cell viability in a dose- and time-dependent manner, triggered a stringent G1 cell cycle arrest, and induced cell apoptosis of glioma U87 cells. Tube formation assays showed that DHA significantly decreased glioma cell tube formation in human umbilical vein endothelial cell (HUVC), and suppressed vascular endothelial growth factor (VEGF) mRNA expression and its release in U87 cells. In addition, wound-scratch assay and martrigel-transwell showed that DHA decreased U87 cell invasion and migration in vitro. These results indicated that DHA might be a valuable candidate for treatment of human glioma.   Key words: Dihydroartemisinin, glioma, proliferation, invasion, angiogenesis.

[1]  A. Arbab.  Activation of alternative pathways of angiogenesis and involvement of stem cells following anti-angiogenesis treatment in glioma. , 2012, Histology and histopathology.

[2]  J. Held-Feindt,et al.  Lost in disruption: role of proteases in glioma invasion and progression. , 2012, Biochimica et biophysica acta.

[3]  A. Silvani,et al.  Decrease in circulating endothelial progenitor cells in treated glioma patients , 2012, Journal of Neuro-Oncology.

[4]  Santosh Kesari,et al.  Understanding glioblastoma tumor biology: the potential to improve current diagnosis and treatments. , 2011, Seminars in oncology.

[5]  X. Pang,et al.  Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase. , 2011, International immunopharmacology.

[6]  C. Houle.  Neuropathology Standards , 2011, Toxicologic pathology.

[7]  P. Haninec,et al.  [Vascular endothelial growth factor]. , 2011, Ceskoslovenska fysiologie.

[8]  J. An,et al.  Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells , 2010, Cancer biology & therapy.

[9]  Ji-hui Du,et al.  Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo , 2009, Cancer Chemotherapy and Pharmacology.

[10]  N. Ferrara.  Vascular Endothelial Growth Factor , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[11]  S. Doublier,et al.  Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium‐dependent activation of HIF‐1α and P‐glycoprotein overexpression , 2009, British journal of pharmacology.

[12]  G. Firestone,et al.  Artemisinin Blocks Prostate Cancer Growth and Cell Cycle Progression by Disrupting Sp1 Interactions with the Cyclin-dependent Kinase-4 (CDK4) Promoter and Inhibiting CDK4 Gene Expression* , 2009, Journal of Biological Chemistry.

[13]  Tongsheng Chen,et al.  Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells , 2009, Journal of Biomedical Science.

[14]  Katherine Holmes,et al.  Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. , 2007, Cellular signalling.

[15]  Pieter Wesseling,et al.  Diffuse glioma growth: a guerilla war , 2007, Acta Neuropathologica.

[16]  Jun Lee,et al.  Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells. , 2007, Vascular pharmacology.

[17]  S. Fan,et al.  Dihydroartemisinin is an inhibitor of ovarian cancer cell growth , 2007, Acta Pharmacologica Sinica.

[18]  Jun Lee,et al.  Dihydroartemisinin downregulates vascular endothelial growth factor expression and induces apoptosis in chronic myeloid leukemia K562 cells , 2005, Cancer Chemotherapy and Pharmacology.

[19]  Hui-jun Zhou,et al.  Antimalarial dihydroartemisinin also inhibits angiogenesis , 2004, Cancer Chemotherapy and Pharmacology.

[20]  S. Meshnick,et al.  Artemisinin: mechanisms of action, resistance and toxicity. , 2002, International journal for parasitology.