Oligosaccharide G19 inhibits U-87 MG human glioma cells growth in vitro and in vivo by targeting epidermal growth factor (EGF) and activating p53/p21 signaling

G19 is a novel homogeneous sulfated oligosaccharide, prepared from Grateloupia filicina (G. filicina). In the present study, we firstly reported that oligosaccharide G19 exhibited a doseand time-dependent anti-proliferation effect against U-87 MG human glioma cells. Further studies indicated that G19 strongly bound to epidermal growth factor (EGF), suppressed epidermal growth factor receptor (EGFR) phosphorylation and interrupted the phosphatidylinositol-3 kinase (PI3K)/Akt pathway in the cancer cells. Moreover, G19 elevated intracellular reactive oxygen species (ROS) levels and caused endogenous DNA damage. These actions were associated with activation of ataxia telangiectasia-mutated (ATM)/checkpoint kinase 2 (Chk2) pathway. The down-regulation of MDM2 with stabilizing p53 and the nuclear location of p21 were induced by G19 to cause cell cycle arrest and apoptosis to some extent. Meanwhile, intrinsic mitochondrial pathway and extrinsic death receptor pathway were involved in G19-mediated apoptosis. Pre-treatment with free radical scavenger N-acetyl-L-cysteine (NAC) nearly completely inversed G19-induced cell growth inhibition, cell cycle arrest and apoptosis in U-87 MG cells. Importantly, G19 could inhibit the growth of U-87 MG tumor cells xenograft in nude mice. The results suggested that G19 could be served as a new targeting drug candidate for human glioma treatment.