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Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches.
Rizvi, Syed Mohd Danish; Almazni, Ibrahim A; Moawadh, Mamdoh S; Alharbi, Zeyad M; Helmi, Nawal; Alqahtani, Leena S; Hussain, Talib; Alafnan, Ahmed; Moin, Afrasim; Elkhalifa, AbdElmoneim O; Awadelkareem, Amir Mahgoub; Khalid, Mohammad; Tiwari, Rohit Kumar.
Afiliação
  • Rizvi SMD; Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Ha'il, Saudi Arabia.
  • Almazni IA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia.
  • Moawadh MS; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
  • Alharbi ZM; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
  • Helmi N; Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
  • Alqahtani LS; Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
  • Hussain T; Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha'il, Ha'il, Saudi Arabia.
  • Alafnan A; Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha'il, Ha'il, Saudi Arabia.
  • Moin A; Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Ha'il, Saudi Arabia.
  • Elkhalifa AO; Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Ha'il, Saudi Arabia.
  • Awadelkareem AM; Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Ha'il, Saudi Arabia.
  • Khalid M; Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
  • Tiwari RK; Department of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Gautam Budh Nagar, India.
Front Chem ; 12: 1352009, 2024.
Article em En | MEDLINE | ID: mdl-38435669
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Front Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Arábia Saudita

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Front Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Arábia Saudita