title: Low arsenite concentrations induce cell proliferation via activation of VEGF signaling in human neuroblastoma SH-SY5Y cells.
abstract: Arsenic widely contaminates the environment, especially in drinking water. Although it is a known carcinogen in humans, its carcinogenic mechanism has not yet been clarified. Here, we demonstrated that a low concentration of arsenite treatment induced proliferation of human neuroblastoma SH-SY5Y cells as indicated by increases in cell viability and BrdU incorporation. Additionally, arsenite increased VEGF expression and secretion. Inhibition of VEGF-induced signaling by SU4312, the inhibitor of VEGF receptor 2 kinase, and by treatment with anti-VEGF antibody blocked arsenite-induced increases in cell proliferation. Moreover, arsenite caused activation of ERK, a key signaling molecule involved in cell proliferation, and this activation was attenuated by SU4312, suggesting that ERK activation contributes to VEGF-mediated cell proliferation induced by arsenite. Collectively, the present study reveals that a mechanism underlying arsenic-induced cell proliferation may be through induction and activation of VEGF signaling, and this may subsequently contribute to tumor formation.
authors: Laboratory of Pharmacology, Chulabhorn Research Institute, 54 Moo 4 Vibhavadee-Rangsit Highway, Bangkok 10210, Thailand.
authors: Piyajit
authors: P
authors: Watcharasit
authors: Daranee
authors: D
authors: Visitnonthachai
authors: Sumitra
authors: S
authors: Suntararuks
authors: Apinya
authors: A
authors: Thiantanawat
authors: Jutamaad
authors: J
authors: Satayavivad
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018053:Arsenites; D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases; C015001:arsenite