Apparently, down-regulation of Fas is mediated by epigenetic mechanisms in human colon carcinoma cells since combinational therapy with DNMT and HDAC inhibitors synergistically activate Fas transcription, as well as pro-apoptotic genes such as BNIP3 and Bik, thereby resulting in increased CRC cell sensitivity to apoptosis induction in vitro and growth inhibition in vivo [228]. Here, BIK is linked to colorectal carcinoma.