VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells
Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nucl...
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| Format: | Article |
| Language: | English |
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Golestan University of Medical Sciences
2023-01-01
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| Series: | Medical Laboratory Journal |
| Subjects: | |
| Online Access: | http://mlj.goums.ac.ir/article-1-1485-en.html |
| _version_ | 1797971456206831616 |
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| author | mohadese namjoo hosein ghafoori Mohsen Asghari |
| author_facet | mohadese namjoo hosein ghafoori Mohsen Asghari |
| author_sort | mohadese namjoo |
| collection | DOAJ |
| description | Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosphorylation. The vascular endothelial growth factor receptor-2 (VEGFR-2) suppression could result in apoptosis induction. Therefore, targeting these pathways via VEGFR-2 inhibitors might have therapeutic potential for cancer treatment. It has been indicated that an antagonist peptide of VEGF, referred to as VGB3, could neutralize and recognize VEGFR2 in the tumoral and endothelial cells. This study aimed to induce apoptosis in human umbilical vein endothelial cells (HUVEC) cells through the inhibition of these signaling pathways.
Methods: Effects of different concentrations of VGB3 (1-200 ng/ml) were evaluated on the viability of HUVEC cells using MTT assay. In addition, downstream signaling pathways in HUVE cells were evaluated through quantitative assessment of protein expression via western blotting.
Results: The results demonstrated that VGB3 treatment inhibited the growth of HUVEC cells. Moreover, Bcl-2 was decreased in the cells treated with the VGB3 compared to the control. Furthermore, VGB3 significantly enhanced the cleaved-caspase7 levels, which is an indicator of apoptosis progression. Altogether, VGB3 enhanced apoptosis in HUVEC cells.
Conclusion: Our results indicate that the peptide might be a potential candidate for antitumor therapy via inhibiting the NF-κB pathway. |
| first_indexed | 2024-04-11T03:32:56Z |
| format | Article |
| id | doaj.art-f45de473646c4b8c825c0be3496d062e |
| institution | Directory Open Access Journal |
| issn | 2538-4449 |
| language | English |
| last_indexed | 2024-04-11T03:32:56Z |
| publishDate | 2023-01-01 |
| publisher | Golestan University of Medical Sciences |
| record_format | Article |
| series | Medical Laboratory Journal |
| spelling | doaj.art-f45de473646c4b8c825c0be3496d062e2023-01-02T06:11:46ZengGolestan University of Medical SciencesMedical Laboratory Journal2538-44492023-01-01171612VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cellsmohadese namjoo0hosein ghafoori1Mohsen Asghari2 Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran 1417614411, Iran Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosphorylation. The vascular endothelial growth factor receptor-2 (VEGFR-2) suppression could result in apoptosis induction. Therefore, targeting these pathways via VEGFR-2 inhibitors might have therapeutic potential for cancer treatment. It has been indicated that an antagonist peptide of VEGF, referred to as VGB3, could neutralize and recognize VEGFR2 in the tumoral and endothelial cells. This study aimed to induce apoptosis in human umbilical vein endothelial cells (HUVEC) cells through the inhibition of these signaling pathways. Methods: Effects of different concentrations of VGB3 (1-200 ng/ml) were evaluated on the viability of HUVEC cells using MTT assay. In addition, downstream signaling pathways in HUVE cells were evaluated through quantitative assessment of protein expression via western blotting. Results: The results demonstrated that VGB3 treatment inhibited the growth of HUVEC cells. Moreover, Bcl-2 was decreased in the cells treated with the VGB3 compared to the control. Furthermore, VGB3 significantly enhanced the cleaved-caspase7 levels, which is an indicator of apoptosis progression. Altogether, VGB3 enhanced apoptosis in HUVEC cells. Conclusion: Our results indicate that the peptide might be a potential candidate for antitumor therapy via inhibiting the NF-κB pathway.http://mlj.goums.ac.ir/article-1-1485-en.htmlapoptosisnf-kappa bvegfr-2 |
| spellingShingle | mohadese namjoo hosein ghafoori Mohsen Asghari VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells Medical Laboratory Journal apoptosis nf-kappa b vegfr-2 |
| title | VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells |
| title_full | VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells |
| title_fullStr | VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells |
| title_full_unstemmed | VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells |
| title_short | VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells |
| title_sort | vgb3 induces apoptosis by inhibiting phosphorylation of nf κb p65 at serine 536 in the human umbilical vein endothelial cells |
| topic | apoptosis nf-kappa b vegfr-2 |
| url | http://mlj.goums.ac.ir/article-1-1485-en.html |
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