These results suggest that inhibition of NR4A1-mediated transcriptional activity was involved in the anticancer effects of fangchinoline, and fangchinoline represents a novel class of mechanism-based anticancer agents targeting NR4A1 that is overexpressed in pancreatic cancer.
The NR4A1 receptor is pro-oncogenic, regulates the ROS/endoplasmic reticulum stress pathways, and inactivation of the receptor represents a novel pathway for inducing cell death in pancreatic cancer.
1,1-Bis(3'-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH3) activates the orphan receptor nerve growth factor-induced Balpha (Nur77) in cancer cells, and in this study, DIM-C-pPhOCH3 decreased Panc1 pancreatic cancer cell survival and arrested cells in G0-G1.