Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer

Principal mechanism of apoptosis activation. (A) Activation of extrinsic pathway occurs through ligand binding to death receptors (FAS, TRAIL-R, or TNFR1), subsequently mediates bind of adapter proteins (FADD or TRADD) building DISC, activating caspase-8/-10 and -3. (B) Several stimuli trigger intrinsic pathway like cytokine deprivation, increase generation of ROS, DNA damage, and ER stress (blue arrow), causing MOMP that leads to the release of the mitochondrial proteins [cytochrome c (red dots), Smac (blue dots)], and subsequent activation of initiator caspase-9 and executioners caspases-3, -6, and -7 concluding in apoptosis. (C) There is crosstalk between the extrinsic and intrinsic pathways through the cleavage of caspase-8, which generates a tBid. tBid triggers MOMP, amplifying the apoptotic signal. FAS: Fas cell surface death receptor. TRAIL-R: TNF-related apoptosis-inducing ligand receptor. TNFR1: TNF receptor superfamily member 1A. FADD: FAS-associated death domain protein. TRADD: TNFR-associated death domain protein. DISC: Death-inducing signaling complex. ROS: Reactive oxygen species. DNA: Deoxyribonucleic acid. ER: Endoplasmic reticulum. MOMP: Mitochondrial outer membrane permeabilization. tBid: Truncated form of Bid.

Publication

The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer. (2023) Mayra Montecillo-Aguado, et al. Int J Mol Sci. 2023 Jul;24(14):11691. Figure: F1. Homo sapiens

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