A Synthetic Dl-nordihydroguaiaretic Acid (Nordy), Inhibits Angiogenesis, Invasion and Proliferation of Glioma Stem Cells Within a Zebrafish Xenotransplantation Model

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jan 24

PMID 24454929

Citations 15

Authors

Xiaojun Yang

Wei Cui

Shicang Yu

Chuan Xu

Guilai Chen

Ai Gu

Tingting Li

Youhong Cui

Xia Zhang

Xiuwu Bian

Affiliations

Soon will be listed here.

Abstract

The zebrafish (Danio rerio) and their transparent embryos represent a promising model system in cancer research. Compared with other vertebrate model systems, we had previously shown that the zebrafish model provides many advantages over mouse or chicken models to study tumor invasion, angiogenesis, and tumorigenesis. In this study, we systematically investigated the biological features of glioma stem cells (GSCs) in a zebrafish model, such as tumor angiogenesis, invasion, and proliferation. We demonstrated that several verified anti-angiogenic agents inhibited angiogenesis that was induced by xenografted-GSCs. We next evaluated the effects of a synthetic dl-nordihydroguaiaretic acid compound (dl-NDGA or "Nordy"), which revealed anti-tumor activity against human GSCs in vitro by establishing parameters through studying its ability to suppress angiogenesis, tumor invasion, and proliferation. Furthermore, our results indicated that Nordy might inhibit GSCs invasion and proliferation through regulation of the arachidonate 5-lipoxygenase (Alox-5) pathway. Moreover, the combination of Nordy and a VEGF inhibitor exhibited an enhanced ability to suppress angiogenesis that was induced by GSCs. By contrast, even following treatment with 50 µM Nordy, there was no discernible effect on zebrafish embryonic development. Together, these results suggested efficacy and safety of using Nordy in vivo, and further demonstrated that this model should be suitable for studying GSCs and anti-GSC drug evaluation.

Citing Articles

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