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Closantel Suppresses Angiogenesis and Cancer Growth in Zebrafish Models
Xiao-Yu Zhu1,2, Bo Xia2, Hong-Cui Liu2
11 Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Wenzhou Medical University , Wenzhou, P.R. China .
Assay and Drug Development Technologies
|April 6, 2016
Summary
Closantel, an antiparasitic drug, demonstrates significant antiangiogenic and anticancer effects in zebrafish models. This finding suggests its potential as a novel therapeutic for various cancers in both animals and humans.
Area of Science:
- Vascular biology and drug discovery
- Zebrafish models for high-throughput screening
- Oncology and therapeutic targets
Background:
- Angiogenesis is a critical process in diseases like cancer and age-related macular degeneration.
- Zebrafish offer a powerful vertebrate model for efficient drug discovery.
- Identifying novel therapeutic agents for angiogenesis-dependent diseases is a key research area.
Purpose of the Study:
- To screen a drug library using zebrafish to identify compounds with antiangiogenic activity.
- To evaluate the antiangiogenic and anticancer potential of identified compounds, particularly Closantel.
- To investigate Closantel's efficacy in preclinical cancer models.
Main Methods:
- Utilized the transgenic Tg (fli1a:EGFP) zebrafish line for high-throughput screening.
- Screened the U.S. Drug Collection Library to identify antiangiogenic compounds.
- Quantified antiangiogenic activity using IC50 values and assessed anticancer effects in zebrafish xenograft models.
Main Results:
- Identified 11 existing drugs with antiangiogenic properties from the screened library.
- Closantel exhibited potent antiangiogenic activity in zebrafish, with IC50 values of 1.69 μM and 1.45 μM.
- Closantel significantly suppressed the growth of human lymphoma, cervical, pancreatic, and liver cancers in zebrafish xenografts.
Conclusions:
- Closantel possesses significant antiangiogenic and anticancer effects, validated in zebrafish models.
- Closantel is a promising drug candidate for treating various animal and human cancers.
- Further research is warranted to elucidate the precise mechanisms underlying Closantel's therapeutic actions.
