Novel perspective in pancreatic cancer therapy: Targeting ferroptosis pathway

Table 1 Features of ferroptosis and other forms of regulated cell death

	Ferroptosis	Necrosis	Apoptosis	Autophagy
Morphological features	Condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, and outer mitochondrial membrane rupture	Organelle swelling, plasma membrane damage, cell disruption	Cell membrane foaming, cell shrinkage and the formation of apoptotic bodies	Cytoplasm vacuolization, formation of autophagosomes and removal of substances through lysosomes
Biochemical features	Iron accumulation; lipid peroxidation; glutaminolysis	Activation of RIPK1, RIPK3, and MLKL; activation of inflammasome and release of pro-inflammatory cytokines	DNA fragmentation; Caspases cascade activation; Ca2+/mg2+ -dependent endogenous nuclease and calpain activation	MAP1LC3B-I to MAP1LC3B-II conversion; increased autophagic flux and lysosomal

Table 2 Ferroptosis inducers in pancreatic ductal adenocarcinoma

Inducers	Target	Inhibited by	Ref.
Erastin	System XC-/GPX4	CPX	Yang et al[18]
Sulfasalazine	System XC-	β-ME, CHX, DFO, Fer-1, NAC, or Trolox	Kim et al[38,68]
Sorafenib	System XC-	DFO, Fer-1, Trolox, or VE	Lachaier et al[37]
Artesunate	System XC-	DFO or Fer-1	Xie et al[9]
RSL3	GPX4	CPX, DFO, Ebs, Fer-1, Lip-1, Trolox, or U0126	Yang et al[18]
Rapamycin	GPX4	Lip-1	Liu et al[60]
FIN56	GPX4	DFO, BSO and α-Toc	Liang et al[68]
FINO2	GPX4/Iron	β-ME or Fer-1	Liang et al[68]
Piperlongumine	GPX4	Fer-1, lip-1, CPX and DFO	Yamaguchi et al[63]
Ruscogenin	Iron	DFO, FAC	Song et al[59]
Irisin	Iron, ROS, and glutathione depletion	Not mentioned	Yang et al[64]

α-Toc: α-tocopherol; β-ME: β-mercaptoethanol; BSO: Buthionine sulfoximine; CHX: Cycloheximide; CPX: Ciclopirox olamine; DFO: Iron chelator deferoxamine; Ebs: Ebselen; FAC: Ferric ammonium citrate. Fer-1: Ferrostatin-1; Lip-1: Liproxstatin-1; NAC: N-acetylcysteine; VE: Vitamin E.