Low arsenite concentrations induce cell proliferation via activation of VEGF signalling in human neuroblastoma SH-SY5Y cells

Arsenic (As) widely contaminates the environment, especially in drinking water. Although it is a known carcinogen in humans, its carcinogenic mechanism has not yet been clarified. In this study, the authors 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. Additional, arsenite increased VEGF expression and secretion. Inhibition of VEGF-induced signalling 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 signalling 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 signalling, and this may subsequently contribute to tumour formation.

Authors: Watcharasit Piyajit; Visitnonthachai Daranee; Suntararuks Sumitra; Thiantanawat Apinya; Satayavivad Jutamaad ;Full Source: Environmental Toxicology and Pharmacology [online computer file] 2012, 33(1), 53-59 (Eng) ;