Dianhydrogalactitol, a potential multitarget agent, inhibits glioblastoma migration, invasion, and angiogenesis.

Abstract

The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in glioblastoma have not been elucidated. Here we show that DAG could inhibit the migration and invasion of U251 cell line by inhibiting matrix metalloproteinase-2 (MMP2) expression. Furthermore, DAG could also inhibit tumor angiogenesis in vitro as well as in the zebrafish model. Mechanistic studies reveal that DAG inhibited both VEGFR2 and FGFR1 pathways. Our results suggest that DAG may be a potential multitarget agent that can inhibit tumor migration, invasion, and angiogenesis, and the anti-angiogenic effects may be involved in dual-suppression VEGF/VEGFR2 and FGF2/FGFR1 signal pathways.

• Authors: Xia Jiang, Yinmei Huang, Xiaojie Wang, Qiaofang Liang, Yingjie Li, Fuji Li, Xuanhao Fu, Chonghuan Huang, Huagang Liu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 91 Pg. 1065-1074 (Jul 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28525947 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• CEP43 protein, human
• Proto-Oncogene Proteins
• Vascular Endothelial Growth Factor A
• Dianhydrogalactitol
• Vascular Endothelial Growth Factor Receptor-2
• Matrix Metalloproteinase 2

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Dianhydrogalactitol (pharmacology)
• Glioblastoma (drug therapy, metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Neoplasm Invasiveness (pathology)
• Neovascularization, Pathologic (drug therapy, metabolism)
• Proto-Oncogene Proteins (metabolism)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)
• Zebrafish