Evaluation of anticancer compounds activity and toxicity in zebrafish model

Abstract

Zebrafish (Danio rerio) is an excellent model for studying toxicity and biological activities of novel compounds with anticancer potential. This model is widely utilized in biological research as it is comparable to human counterpart both molecularly and pathologically. As an in vivo system for toxicology, zebrafish has numerous advantages such as rapid and ex utero development, transparent embryos in early stages, high fecundity allowing high-throughput screening and cost effectiveness. Furthermore, evaluation of known toxic compounds in zebrafish revealed 63–100% predictability making zebrafish a very useful tool for studying toxic effects [1, 2]. In addition, embryonic zebrafish cancer models can be used for studying pathways and processes relevant to human malignancy including tumor-induced angiogenesis, tumor invasiveness, proliferation and migration. These models can be generated using transgenesis, gene inactivation, xenotransplantation, and cancerogenic induction. Herein, we present the results obtained in zebrafish toxicity studies of siramesine, a sigma receptor agonist with anticancer potential. Concentration dependent increase in lethality, induced by siramesine treatment, was observed in zebrafish embryos at 24 h post fertilization (hpf), 48 hpf and 72 hpf. Various concentration dependent toxic effects on embryo development were also observed, as well as decreased hatching rate in embryos treated with 5 µM and 10 µM siramesine at 72 hpf. Results obtained in zebrafish cancer model generated via xenotransplantation are also presented. This model was utilized to study the effect of Src tyrosine kinase inhibitor pro-LDS10 on the invasiveness of microinjected human glioblastoma cell line U87. Treatment with 5 µM pro-LDS10 resulted in significant reduction of U87 migratory potential at 4 days post injection.