Glioblastoma (GBM) is the most aggressive brain cancer. Curcumin, a natural dietary polyphenol extracted from Curcuma longa L, has a demonstrated promising outcome against the GBM. Many molecular targets of curcumin are still undefined. Our lab is focused on the functional role of FAT1 which is a transmembrane protein and found to have oncogenic role in GBM. This study is designed to analyze the regulation of FAT1 expression by curcumin.
U87MG cells were treated with Curcumin (5uM, 10uM and 20uM) for 24 hours, PDTC (Pyrrolidine dithiocarbamate) (5uM and 10uM) for 1 hour and TNFα (100ng/ml) for 24 hours. FAT1 promoter pGL3F1 [1kb; -200bp/+848bp from transcription start site (TSS) (+1)] was cloned in luciferase vector (pGL3Basic) and promoter activity was analysed in U87MG, A172, and U373MG. Characterization of NFkB binding sites was done by FAT1 deletion constructs (5’ and 3’ NFkB site deletion), site directed mutagenesis (SDM) and ChIP assay. FAT1 and NFkB expression were correlated in GBM tumors (n = 16) and TCGA GBM data set.
Our in-vitro and GBM tumor analysis for the first time confirms the regulation of FAT1 by curcumin via NFkB transcription factor in glioblastoma and also validating a novel link between NFkB and FAT1.
AIIMS
Indian council for medical research (ICMR)
All authors have declared no conflicts of interest.