Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches
Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. Duri...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2024.1352009/full |
| _version_ | 1797305294714306560 |
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| author | Syed Mohd Danish Rizvi Ibrahim A. Almazni Mamdoh S. Moawadh Zeyad M. Alharbi Nawal Helmi Leena S. Alqahtani Talib Hussain Ahmed Alafnan Afrasim Moin AbdElmoneim O. Elkhalifa Amir Mahgoub Awadelkareem Mohammad Khalid Rohit Kumar Tiwari |
| author_facet | Syed Mohd Danish Rizvi Ibrahim A. Almazni Mamdoh S. Moawadh Zeyad M. Alharbi Nawal Helmi Leena S. Alqahtani Talib Hussain Ahmed Alafnan Afrasim Moin AbdElmoneim O. Elkhalifa Amir Mahgoub Awadelkareem Mohammad Khalid Rohit Kumar Tiwari |
| author_sort | Syed Mohd Danish Rizvi |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM. |
| first_indexed | 2024-03-08T00:23:49Z |
| format | Article |
| id | doaj.art-63f59d0b78e341ecb05566dd387d9261 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-03-08T00:23:49Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-63f59d0b78e341ecb05566dd387d92612024-02-16T04:17:10ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462024-02-011210.3389/fchem.2024.13520091352009Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approachesSyed Mohd Danish Rizvi0Ibrahim A. Almazni1Mamdoh S. Moawadh2Zeyad M. Alharbi3Nawal Helmi4Leena S. Alqahtani5Talib Hussain6Ahmed Alafnan7Afrasim Moin8AbdElmoneim O. Elkhalifa9Amir Mahgoub Awadelkareem10Mohammad Khalid11Rohit Kumar Tiwari12Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi ArabiaDepartment of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi ArabiaDepartment of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaDepartment of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Ha’il, Saudi ArabiaDepartment of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Ha’il, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi ArabiaDepartment of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Gautam Budh Nagar, IndiaGlioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM.https://www.frontiersin.org/articles/10.3389/fchem.2024.1352009/fullanti-cancerbenzophenonegarcinolglioblastoma multiformeNF-κB |
| spellingShingle | Syed Mohd Danish Rizvi Ibrahim A. Almazni Mamdoh S. Moawadh Zeyad M. Alharbi Nawal Helmi Leena S. Alqahtani Talib Hussain Ahmed Alafnan Afrasim Moin AbdElmoneim O. Elkhalifa Amir Mahgoub Awadelkareem Mohammad Khalid Rohit Kumar Tiwari Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches Frontiers in Chemistry anti-cancer benzophenone garcinol glioblastoma multiforme NF-κB |
| title | Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches |
| title_full | Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches |
| title_fullStr | Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches |
| title_full_unstemmed | Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches |
| title_short | Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches |
| title_sort | targeting nf κb signaling cascades of glioblastoma by a natural benzophenone garcinol via in vitro and molecular docking approaches |
| topic | anti-cancer benzophenone garcinol glioblastoma multiforme NF-κB |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2024.1352009/full |
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