Since paracrine interaction in the TME plays a crucial role in stimulating the tumor progression process linked with apoptosis inhibition, in the present study we investigated the potential role of Calebin A in targeting the NF-κB signaling pathway to suppress the cross-talk in the TME and to stimulate apoptosis in CRC in a multicellular pro-inflammatory TME, in vitro. This evidence concerns the gene NFKB1 and colorectal carcinoma.