Table 2.

Necroptosis mechanism in cancer disease.

Protein	Up/down	Description	Article related to necroptosis	References
TNF	Up	Tumor necrosis factor	Fisetin significantly increases TNF and IK expression while decreasing pNF-, and pIK expression	[35]
RIPK1 and RIPK3	Up	Receptor-interacting protein kinase-1 and 3	In the presence of ZVAD, MCF-7 cells express substantially more RIPK1 and RIPK3 in response to Que than in the absence of ZVAD	[33]
TNFR1	Up	TNF's receptor following the formation of two TNFR complexes	Cell survival, apoptosis, or necroptosis can result from TNFR1 stimulation caused by damage, cellular stress, or infection	[8, 36]
			TNF-α, TNFR1, and necroptosis protein expression are all inhibited by PPO, indicating that PPO can protect neurons by preventing TNF-α-induced necroptosis	[37]
FADD	Up	Fas-associated protein with death domain (FADD). Activation of MLKL	Necroptosis is caused by caspase-8, FADD, and RIPK3 (complex IIa/b)	[36]
			FADD expression in HepG2 is reduced by fisetin treatment. FADD protects intestinal epithelial cells from RIP3-induced cell necrosis	[35]
MLKL	Up	MLKL (mixed lineage kinase like) after rapid plasma membrane rupture and inflammatory response via DAMP and cytokine release	M1 CM significantly increases expression levels of MLKL, RIPK3, and p-MLKL after quercetin treatment	[36, 38]