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Table 1 Radiotherapy induces different cell fate decisions in tumor cells

From: Radiotherapy modulates tumor cell fate decisions: a review

Type of CFD

CFD characteristics

Features

Key factors

References

Apoptosis

PCD

Cell shrinkage, chromatin condensation, nuclear fragmentation, plasma membrane blebbing, production of apoptotic bodies

Caspase ↑; p53 ↑; Bcl-2 ↓; BAX ↑; PUMA ↑; NOXA ↑

[31, 32]

Necrosis

Non-PCD

DNA damage results in cell swelling, rupture of the plasma membrane, and outflow of cellular contents, followed by inflammation and damage

ATP ↓; NAD ↓; Ca2+ ↑

[13, 14, 36,37,38]

Necroptosis

PCD

A MLKL- dependent PCD with a necrotic morphology

Caspase-8 ↓; RIPK1 ↑; RIPK3 ↑; MLKL ↑

[47]

Pyroptosis

PCD

A GSDM-dependent PCD with a necrotic morphology

NLRP3 ↑; AIM2 ↑; caspase-1 ↑; GSDMD ↑; IL-18 ↑; IL-1β ↑

[51, 52, 55]

Ferroptosis

PCD

An iron-dependent lipid peroxidation-induced PCD with a necrotic morphology

Fe2+ ↑; SLC7A11-GSH-GPX4 ↓ PUFA-PL ↑; ACSL4 ↑; LPCAT3 ↑; NAD(P)H-FSP1-CoQ ↓

[64, 73, 74, 84]

Autophagy

PCD

Lysosome degrades autophagosomes that engulf cytoplasmic components, and can induce autophagic cell death

PI3K-AKT-mTORC1; p53; p73; E2F1

[94, 95]

Senescence

Non-lethal process

A state in which cells lose their ability to proliferate

p53-p21 ↓; p16INK4a-pRB ↓

[101, 105, 107]

Mitotic catastrophe

Non-lethal process

Abnormal nuclear morphology, multi nucleated, multi micro-nucleated giant cells

P53-p21 ↓; CDK1-cyclin ↑; CDK2-cyclin E/A ↑

[118,119,120]

Cuproptosis

PCD

An PCD dependent on copper and protein acylation in TCA cycle with a necrotic morphology

Cu+ ↑; FDX1 ↑; LIAS ↑; DLAT ↑

[124, 125]

  1. ACSL4, acyl-CoA synthetase long-chain 4; BAX, Bcl-2-associated X protein; Bcl-2, B-cell chronic lymphocytic leukemia/lymphoma-2; CDK, cyclin-dependent kinase; CFD: cell fate decision; FDX1: ferredoxin 1; FSP1: ferroptosis suppressor protein 1; GSDM, gasdermin; LPCAT3, lysophosphatidylcholine acyltransferase 3; MLKL, mixed lineage kinase domain-like protein; NAD, nicotinamide adenine dinucleotide; PCD: programmed cell death; PUFA-PL, phospholipid containing polyunsaturated fatty acid chain; PUMA, p53 upregulated modulator of apoptosis; RIPK, receptor-interacting serine/threonine-protein kinase; SLC7A11, solute carrier family 7 member 11; TCA, tricarboxylic acid