1. A Synthetic dl-Nordihydroguaiaretic acid (Nordy), Inhibits Angiogenesis, Invasion and Proliferation of Glioma Stem Cells within a Zebrafish Xenotransplantation Model
- Author
-
Xia Zhang, Xiu-Wu Bian, Ai Gu, You-Hong Cui, Chuan Xu, Wei Cui, Gui-lai Chen, Xiaojun Yang, Ting-ting Li, and Shi-cang Yu
- Subjects
Pathology ,Angiogenesis ,Cellular differentiation ,Tumor Physiology ,Cancer Treatment ,lcsh:Medicine ,medicine.disease_cause ,Neovascularization ,Drug Discovery ,Molecular Cell Biology ,Basic Cancer Research ,AC133 Antigen ,lcsh:Science ,Zebrafish ,Multidisciplinary ,biology ,Neovascularization, Pathologic ,Brain Neoplasms ,Stem Cells ,Cell Differentiation ,Animal Models ,Glioma ,Cell biology ,Oncology ,Neoplastic Stem Cells ,Medicine ,Stem cell ,medicine.symptom ,Cellular Types ,Research Article ,Biotechnology ,medicine.medical_specialty ,endocrine system ,Drugs and Devices ,animal structures ,Drug Research and Development ,Clinical Research Design ,Antineoplastic Agents ,Model Organisms ,In vivo ,Antigens, CD ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Masoprocol ,Neoplasm Invasiveness ,Animal Models of Disease ,Biology ,Cell Proliferation ,Glycoproteins ,Cell growth ,lcsh:R ,fungi ,biology.organism_classification ,Xenograft Model Antitumor Assays ,Receptors, Vascular Endothelial Growth Factor ,Pharmacodynamics ,lcsh:Q ,Carcinogenesis ,Peptides - 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.
- Published
- 2014