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AuthorKheraldine, Hadeel
AuthorHassan, Arij Fouzat
AuthorAlhussein, Hashim
AuthorAl-Thawadi, Hamda
AuthorVranic, Semir
AuthorAl Moustafa, Ala-Eddin
Available date2024-03-05T13:48:49Z
Publication Date2023-12-27
Publication NameBiomolecules and Biomedicine
Identifierhttp://dx.doi.org/10.17305/bb.2023.9869
CitationEffects of neratinib on angiogenesis and the early stage of the embryo using chicken embryo as a model. Biomol Biomed [Internet]. 2023 Dec. 27 [cited 2024 Mar. 5];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/9869
ISSN2831-0896
URIhttp://hdl.handle.net/10576/52706
AbstractAngiogenesis 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.
SponsorThisresearchwasfundedbyQatarUniversity[QUCP-CMED-2021-1] and Qatar National Research Fund [ECRA03-003-3-002].
Languageen
Publisherthe Association of Basic Medical Sciences
SubjectNeratinib
angiogenesis
embryogenesis
chorioallantoic membrane (CAM)
tyrosine kinase inhibitor (TKI)
TitleEffects of neratinib on angiogenesis and the early stage of the embryo using chicken embryo as a model.
TypeArticle
ESSN2831-090X
dc.accessType Open Access


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