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Anti-angiogenesis Function of Ononin via Suppressing the MEK/Erk Signaling Pathway
Guowei Gong1, Yuzhong Zheng2, Xiangpeng Kong3
1Department of Bioengineering, Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong 519041, China.
Abstract:
Angiogenesis is a complicated pathological process and plays an important role in modulating tumor development. Flavonoids, sharing the basic functional group with estrogen, have been utilized as chemopreventive agents to inhibit endothelial cell angiogenesis and also suppress tumor cell proliferation. Ononin, also referred to as formononetin-7-O-β-d-glucoside, is one of the bioactive chemicals found within many functional food or plants. The anticancer functions of ononin have been reported both in vitro and in vivo. However, the anti-angiogenetic properties of ononin have not been reported. The possible efficacies of ononin against angiogenesis was verified in cultured endothelial cells. Ononin suppressed vascular endothelial growth factor (VEGF)-induced HUVEC migration, invasion. and tube formation activity after 48 h. The apoptosis rate and specific markers, i.e., Bax/Bc-2 ratio, cleaved caspase 3/9 (Cl-caspase 3/9), and cytochrome c (Cyto c), were enhanced in the ononin-treated group. On the other hand, the protein expressions levels of hypoxia-inducible factor 1α (HIF-1α), mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK), and vascular endothelial growth factor receptor 2 (VEGFR2) were restricted after ononin treatment for 2 days in VEGF-pretreated endothelial cells. In summary, ononin acts as a candidate for angiogenetic-related disease prevention and treatment.
Insights
Ononin, a plant-derived flavonoid, effectively inhibits angiogenesis, the process crucial for tumor development. This study shows ononin suppresses endothelial cell migration, invasion, and tube formation, offering potential for cancer prevention.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Angiogenesis is a critical pathological process in tumor development.
- Flavonoids, like ononin, are explored for chemopreventive properties.
- Ononin's anti-angiogenic effects remain largely unexplored.
Purpose of the Study:
- To investigate the anti-angiogenic properties of ononin in cultured endothelial cells.
- To elucidate the molecular mechanisms underlying ononin's potential anti-angiogenic effects.
Main Methods:
- Human Umbilical Vein Endothelial Cells (HUVECs) were treated with ononin.
- Assays measured cell migration, invasion, and tube formation.
- Apoptosis markers and key protein expression levels (HIF-1α, MEK/ERK, VEGFR2) were analyzed.
Main Results:
- Ononin significantly suppressed VEGF-induced HUVEC migration, invasion, and tube formation.
- Ononin treatment enhanced apoptosis by increasing the Bax/Bc-2 ratio and cleaved caspase levels.
- Ononin reduced the expression of HIF-1α, MEK/ERK, and VEGFR2 proteins.
Conclusions:
- Ononin exhibits significant anti-angiogenic activity by inhibiting endothelial cell functions.
- Ononin promotes apoptosis and modulates key signaling pathways involved in angiogenesis.
- Ononin represents a potential therapeutic candidate for preventing and treating angiogenesis-related diseases, including cancer.
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