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Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy
Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086168/ https://www.ncbi.nlm.nih.gov/pubmed/37056983 http://dx.doi.org/10.3389/fphar.2023.1150270 |
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author | Velayutham, Naveen Kumar Thamaraikani, Tamilanban Wahab, Shadma Khalid, Mohammad Ramachawolran, Gobinath Abullais, Shahabe Saquib Wong, Ling Shing Sekar, Mahendran Gan, Siew Hua Ebenezer, Angel Jemima Ravikumar, Mrinalini Subramaniyan, Vetriselvan Mat Rani, Nur Najihah Izzati Wu, Yuan Seng Jeyabalan, Srikanth |
author_facet | Velayutham, Naveen Kumar Thamaraikani, Tamilanban Wahab, Shadma Khalid, Mohammad Ramachawolran, Gobinath Abullais, Shahabe Saquib Wong, Ling Shing Sekar, Mahendran Gan, Siew Hua Ebenezer, Angel Jemima Ravikumar, Mrinalini Subramaniyan, Vetriselvan Mat Rani, Nur Najihah Izzati Wu, Yuan Seng Jeyabalan, Srikanth |
author_sort | Velayutham, Naveen Kumar |
collection | PubMed |
description | Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski’s rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future. |
format | Online Article Text |
id | pubmed-10086168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100861682023-04-12 Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy Velayutham, Naveen Kumar Thamaraikani, Tamilanban Wahab, Shadma Khalid, Mohammad Ramachawolran, Gobinath Abullais, Shahabe Saquib Wong, Ling Shing Sekar, Mahendran Gan, Siew Hua Ebenezer, Angel Jemima Ravikumar, Mrinalini Subramaniyan, Vetriselvan Mat Rani, Nur Najihah Izzati Wu, Yuan Seng Jeyabalan, Srikanth Front Pharmacol Pharmacology Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski’s rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future. Frontiers Media S.A. 2023-03-28 /pmc/articles/PMC10086168/ /pubmed/37056983 http://dx.doi.org/10.3389/fphar.2023.1150270 Text en Copyright © 2023 Velayutham, Thamaraikani, Wahab, Khalid, Ramachawolran, Abullais, Wong, Sekar, Gan, Ebenezer, Ravikumar, Subramaniyan, Mat Rani, Wu and Jeyabalan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Velayutham, Naveen Kumar Thamaraikani, Tamilanban Wahab, Shadma Khalid, Mohammad Ramachawolran, Gobinath Abullais, Shahabe Saquib Wong, Ling Shing Sekar, Mahendran Gan, Siew Hua Ebenezer, Angel Jemima Ravikumar, Mrinalini Subramaniyan, Vetriselvan Mat Rani, Nur Najihah Izzati Wu, Yuan Seng Jeyabalan, Srikanth Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy |
title | Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy |
title_full | Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy |
title_fullStr | Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy |
title_full_unstemmed | Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy |
title_short | Stylopine: A potential natural metabolite to activate vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy |
title_sort | stylopine: a potential natural metabolite to activate vascular endothelial growth factor receptor 2 (vegfr2) in osteosarcoma therapy |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086168/ https://www.ncbi.nlm.nih.gov/pubmed/37056983 http://dx.doi.org/10.3389/fphar.2023.1150270 |
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