Effects of neratinib on angiogenesis and the early stage of the embryo using chicken embryo as a model

Authors

  • Hadeel Kheraldine College of Medicine, QU Health, Qatar University, Doha, Qatar
  • Arij Fouzat Hassan College of Pharmacy, QU Health, Qatar University, Doha, Qatar
  • Hashim Alhussain Biomedical Research Center, Qatar University, Doha, Qatar
  • Hamda Al-Thawadi College of Medicine, QU Health, Qatar University, Doha, Qatar
  • Semir Vranic College of Medicine, QU Health, Qatar University, Doha, Qatar
  • Ala-Eddin Al Moustafa College of Medicine, QU Health, Qatar University, Doha, Qatar; Biomedical Research Center, Qatar University, Doha, Qatar; Oncology Department, Faculty of Medicine, McGill University, Montreal, QC, Canada

DOI:

https://doi.org/10.17305/bb.2023.9869

Keywords:

Neratinib, angiogenesis, embryogenesis, chorioallantoic membrane (CAM), tyrosine kinase inhibitor (TKI)

Abstract

Angiogenesis is the process of forming new blood capillaries from pre-existing vessels. Even though it is essential during normal development, it plays a major role in cancer progression. Neratinib is a pan-human epidermal growth factor receptor (HER) inhibitor that has recently been approved for the treatment of HER2-positive breast cancer. However, its effects on angiogenesis and embryogenesis remain unknown. This study examined the antiangiogenic effects of neratinib using the chorioallantoic membrane (CAM) of chicken embryos. We also evaluated neratinib’s toxicity during the early stages of normal development using the chicken embryos, primary embryonic fibroblasts (EFBs), and human umbilical vein endothelial cells (HUVEC). Our findings revealed that neratinib significantly inhibited the CAM angiogenesis compared to controls by reducing vessel percentage area and the average vessel length. Furthermore, neratinib downregulated vascular endothelial growth factor (VEGF), a key mediator of angiogenesis. At lower concentrations, neratinib was well-tolerated during early stages of normal development. Additionally, EFBs treated with neratinib showed no morphological or viability changes when compared to controls. However, at the highest concentration tested, neratinib treatment reduced HUVEC cell viability. This effect may be associated with the dysregulation of key apoptotic genes, including caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 (Bcl2) gene. Our findings indicate a novel potential application of neratinib as an antiangiogenic agent, exhibiting tolerable toxicity in the early stages of embryogenesis.

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Effects of neratinib on angiogenesis and the early stage of the embryo using chicken embryo as a model

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Published

02-05-2024

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Section

Pharmacology

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How to Cite

1.
Effects of neratinib on angiogenesis and the early stage of the embryo using chicken embryo as a model. Biomol Biomed [Internet]. 2024 May 2 [cited 2024 May 20];24(3):575–581. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/9869