However, accumulating evidence indicates that PUMA primarily engages necroptosis under certain circumstances, such as cell death induced by TNF-α and SMAC mimetics in HT29 CRC cells [17], by 5-FU and other antimetabolites in some RIP3-expressing CRC cells [19], and by acetaminophen in mouse hepatocytes [40]. This evidence concerns the gene BBC3 and colorectal carcinoma.