Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches.

Autor: Danish Rizvi, Syed Mohd, 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, Khan, Rehan, Tabrez, Shams
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Zdroj: Frontiers in Chemistry; 2024, p01-12, 12p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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