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 .

Insights

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.

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