AUTHOR=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 

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

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1352009

DOI=10.3389/fchem.2024.1352009

ISSN=2296-2646

ABSTRACT=<p>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 (<italic>p &lt; 0.001</italic>). 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 (<italic>p &lt; 0.001</italic>) 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 Pro<sup>275</sup>, Trp<sup>258</sup>, Glu<sup>225</sup>, and Gly<sup>259</sup> during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death <italic>via</italic> inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM.</p>