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Updated: May 15, 2025
Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
A study to assess the vascular developmental toxicity of anticarcinogen toremifene in zebrafish (Danio rerio)
Juan Liu1, Huiyun Wang1, Chun Yang1
1Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, No. 174, Shazheng Street, Shapingba District, Chongqing 400030, China. tzhu@cqu.edu.cn.
Abstract:
Due to the increasing burden of disease and demand for medicines, more and more pharmaceutical compounds are appearing in the environment. Toremifene (TOR), a first-line drug in the therapy of breast cancer, is widely used in the treatment of related diseases. However, the toxicity assessment of TOR is insufficient. Here, a model organism zebrafish and human umbilical vein endothelial cells (HUVECs) were used to investigate the effects and mechanisms of TOR on angiogenesis. The results showed that TOR exposure reduced hatching and survival rates, and increased the malformation rate. TOR inhibited angiogenesis by inducing nuclear condensation in zebrafish endothelial cells and impeding cell migration, resulting in vascular malformation in zebrafish embryos. TOR disrupted the cytoskeleton, suppressed HUVEC migration, adhesion, activity and division, induced cell cycle arrest, and accelerated apoptosis. qRT-PCR indicated that transcriptional levels of Integrin β1, Rho, ROCK, and MLC-1 reduced in the TOR-exposed groups, and western blot indicated that TOR decreased the contents of Integrin β1, Rho, ROCK, MLC, and pMLC in the Rho/ROCK signaling pathway. Collectively, TOR may disturb endothelial cell behaviors by disrupting the cytoskeleton via the Rho/ROCK signaling pathway, ultimately resulting in abnormal angiogenesis. The study increases awareness of the toxicity of TOR to aquatic organisms and raises public concern about the health risks posed by anti-tumor drugs.
Insights
Toremifene (TOR), a breast cancer drug, harms zebrafish embryos and human cells by disrupting blood vessel formation. This anti-tumor medication impacts endothelial cell behavior and angiogenesis, raising environmental and health concerns.
Area of Science:
- Environmental Toxicology
- Cell Biology
- Pharmacology
Background:
- Pharmaceutical compounds, including Toremifene (TOR), are increasingly detected in the environment.
- TOR is a vital breast cancer therapeutic, but its environmental toxicity is not well-assessed.
Purpose of the Study:
- To investigate the effects and mechanisms of TOR on angiogenesis using zebrafish and human umbilical vein endothelial cells (HUVECs).
- To evaluate the toxicity of TOR to aquatic organisms and potential human health risks.
Main Methods:
- Utilized zebrafish embryos and HUVECs to assess TOR's impact on angiogenesis.
- Examined TOR's effects on cell viability, migration, cell cycle, apoptosis, and the Rho/ROCK signaling pathway via qRT-PCR and Western blot.
Main Results:
- TOR exposure decreased zebrafish hatching and survival rates, increased malformations, and inhibited angiogenesis by affecting endothelial cell nuclear condensation and migration.
- TOR disrupted the cytoskeleton, suppressed HUVEC migration, adhesion, proliferation, induced cell cycle arrest, and apoptosis.
- TOR reduced the expression and content of key proteins in the Rho/ROCK signaling pathway, including Integrin β1, Rho, ROCK, and MLC.
Conclusions:
- TOR disrupts endothelial cell behaviors and angiogenesis by interfering with the cytoskeleton via the Rho/ROCK signaling pathway.
- The study highlights TOR's toxicity to aquatic life and underscores potential health risks associated with anti-tumor drugs in the environment.
