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

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Xia JiangHuagang Liu

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.

Citations

Jun 29, 2018·Expert Opinion on Therapeutic Patents·Matthew HarrisDavid Bailey
May 17, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Xingzhi ZhouShuangping Liu
Oct 23, 2019·Biotechnology for Biofuels·Sujit Sadashiv JagtapChristopher V Rao
Aug 21, 2018·Frontiers in Pharmacology·Simona SestitoSimona Rapposelli

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