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.

Abstract

G19 is a novel homogeneous sulfated oligosaccharide, prepared from Grateloupia filicina. In the present study, we first reported that oligosaccharide G19 exhibited a dose- and time-dependent anti-proliferation effect against U-87 malignant gliomas (MG) human glioma cells. Further studies indicated that G19 strongly bound to epidermal growth factor (EGF), suppressed EGF receptor phosphorylation and interrupted the phosphatidylinositol-3 kinase/Akt pathway in the cancer cells. Moreover, G19 elevated intracellular reactive oxygen species levels and caused endogenous DNA damage. These actions were associated with activation of ataxia-telangiectasia-mutated/checkpoint kinase 2 pathway. The downregulation 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. Pretreatment with free radical scavenger N-acetyl-l-cysteine 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.

• Authors: Hailing Liu, Ling Zhou, Songshan Shi, Ying Wang, Xinyan Ni, Fei Xiao, Shunchun Wang, Ping Li, Kan Ding
• Journal: Glycobiology (Glycobiology) Vol. 24 Issue 8 Pg. 748-65 (Aug 2014) ISSN: 1460-2423 [Electronic] England
• PMID: 24799378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antineoplastic Agents, Phytogenic
• Cyclin-Dependent Kinase Inhibitor p21
• Oligosaccharides
• Tumor Suppressor Protein p53
• Epidermal Growth Factor

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Epidermal Growth Factor (metabolism)
• Glioma (drug therapy, metabolism, pathology)
• Humans
• Molecular Targeted Therapy
• Oligosaccharides (pharmacology)
• Rhodophyta (chemistry)
• Signal Transduction (drug effects)
• Structure-Activity Relationship
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (metabolism)