Isopimpinellin extends antiangiogenic effect through overexpression of miR-15b-5p and downregulating angiogenic stimulators
| Autor: | Sambhavi Bhagavatheeswaran, Anandan Balakrishnan, Vinu Ramachandran, Sambantham Shanmugam |
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| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
Isopimpinellin Angiogenesis Angiogenesis Inhibitors chemistry.chemical_compound Downregulation and upregulation In vivo Cell Movement Furocoumarins Survivin Genetics Human Umbilical Vein Endothelial Cells Animals Humans Molecular Biology Protein kinase B Zebrafish Cell Proliferation Tube formation Chemistry Gene Expression Regulation Developmental General Medicine Hypoxia-Inducible Factor 1 alpha Subunit Up-Regulation Endothelial stem cell MicroRNAs Models Animal Cancer research Proto-Oncogene Proteins c-akt |
| Zdroj: | Molecular biology reports. 49(1) |
| ISSN: | 1573-4978 |
| Popis: | Angiogenesis is the formation of new blood vessels from an existing vasculature through a series of processes such as activation, proliferation, and directed migration of endothelial cells. Angiogenesis is instrumental in the metastatic spread of tumors. Isopimpinellin, a furanocoumarin group of phytochemicals, is an anticarcinogenic agent. However, no studies have proven its antiangiogenic effects. The current study thus aimed to screen the antiangiogenic effect of isopimpinellin. Human Umblical Vein Endothelial Cell (HUVEC) as an in vitro model and zebrafish embryos as an in vivo model was used in this study. The experimental results showed that isopimpinellin effectively inhibited HUVEC proliferation, invasion, migration, and tube formation, which are the key steps in angiogenesis by markedly suppressing the expression of pro-angiogenic genes VEGF, AKT, and HIF-1α. In addition, isopimpinellin exerts its anti-angiogenic effect through the regulation of miR-15b-5p and miR-542-3p. Furthermore, in zebrafish embryos, isopimpinellin inhibited the development of intersegmental vessels (ISVs) through the significant downregulation of all pro-angiogenic genes vegf, vegfr2, survivin, angpt-1, angpt-2, and tie-2. Collectively, these experimental findings offer novel insights into the antiangiogenic nature of isopimpinellin and open new avenues for therapeutic approaches. |
| Databáze: | OpenAIRE |
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