title: Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway.
abstract: Dihydroartemisinin (DHA) is a semi-synthetic derivative of artemisinin, a well-tolerated and effective drug for malaria treatment, and has recently been shown to have antitumorigenic activity. However, the mechanistic basis of these activities in gliomas is unknown. The objective of this study was to evaluate whether DHA inhibits cell proliferation and invasion in glioma cells, and to elucidate the underlying mechanisms. The results demonstrate that DHA treatment significantly inhibited cell proliferation, migration and invasion, as determined using viability, transwell migration, and matrix penetration assays, respectively. Western blot analysis revealed that protein expression levels of a disintegrin and metalloproteinase 17 (ADAM17), and phosphorylated epidermal growth factor receptor and AKT (p-EGFR and p-AKT, respectively), were suppressed by DHA. EGFR and AKT phosphorylation was enhanced by stimulation with the ADAM17 agonist chemokine phorbol myristate acetate. These data suggest that DHA inhibits glioma proliferation and invasion through suppression of ADAM17 and downregulation of EGFR-PI3 K-AKT signaling.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical University, 34# Zhongshan Road, Quanzhou, 362000, Fujian Province, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Chen
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Chen
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Gao
authors.forename: Weipeng
authors.initials: W
authors.lastname: Hu
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; C039060:artenimol; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human