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Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL).

Elmallah MI, Micheau O - Mar Drugs (2015)

Bottom Line: Marine biomass diversity is a tremendous source of potential anticancer compounds.Its selectivity for cancer cells has attracted much attention in oncology.This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Faculty of Science, Helwan University, Ain Helwan, Cairo 11790, Egypt. mohamed_almallah@science.helwan.edu.eg.

ABSTRACT
Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells has attracted much attention in oncology. This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells.

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Schematic representation of apoptosis induced by TRAIL. Binding of TRAIL to its agonistic receptors (DR4 and/or DR5) leads to their oligomerization (1), and the subsequent recruitment of the cytosolic adapter protein FADD through DD homotypic interactions (2). FADD, in turn, enables recruitment of the initial pro-caspase-8/-10 through DED interactions leading to the formation of the so-called DISC (death-inducing signaling complex (3)). Within the DISC, chains of caspase-8/-10 are assembled (4), allowing self-processing of caspase-8/10 and release of their active fragments to the cytosol (5), where they activate, by proteolytic cleavage, effector caspases (6) to execute the apoptotic program (7). Amplification of the signal through the intrinsic pathway is sometimes required when caspase-8 is not sufficiently activated. In this scenario activation of mitochondria is induced by caspase-8/-10 through cleavage of the BH3-only Bcl-2 family protein Bid (8), whose truncated version (tBid) is able to translocate to mitochondria and induce a change of their outer membrane permeability, through Bak and Bax interactions (9), allowing cytochome c release, activation of caspase-9, another initiator caspase able to activate the executioner caspase-3/-7 (10).
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marinedrugs-13-06884-f001: Schematic representation of apoptosis induced by TRAIL. Binding of TRAIL to its agonistic receptors (DR4 and/or DR5) leads to their oligomerization (1), and the subsequent recruitment of the cytosolic adapter protein FADD through DD homotypic interactions (2). FADD, in turn, enables recruitment of the initial pro-caspase-8/-10 through DED interactions leading to the formation of the so-called DISC (death-inducing signaling complex (3)). Within the DISC, chains of caspase-8/-10 are assembled (4), allowing self-processing of caspase-8/10 and release of their active fragments to the cytosol (5), where they activate, by proteolytic cleavage, effector caspases (6) to execute the apoptotic program (7). Amplification of the signal through the intrinsic pathway is sometimes required when caspase-8 is not sufficiently activated. In this scenario activation of mitochondria is induced by caspase-8/-10 through cleavage of the BH3-only Bcl-2 family protein Bid (8), whose truncated version (tBid) is able to translocate to mitochondria and induce a change of their outer membrane permeability, through Bak and Bax interactions (9), allowing cytochome c release, activation of caspase-9, another initiator caspase able to activate the executioner caspase-3/-7 (10).

Mentions: TRAIL agonist receptors contain an intracellular death domain (DD) that enables the assembly of the death-inducing signaling complex (DISC), leading eventually to apoptosis (Figure 1). Like most death ligands of the TNF superfamily, TRAIL binding to its cognate agonistic receptors triggers their aggregation, and with the exception of TNF-R1 [8], subsequent recruitment of the adaptor protein FADD (Fas Associated Death Domain) at the membrane level [9], through DD homotypic interactions (Figure 1). Once associated with TRAIL agonist receptors, FADD in turn enables the recruitment of the initiators caspases, namely caspase-8 and/or caspase-10, through its death effector domain (DED). DED-containing proteins, like proteins harboring DD’s, are able to interact with themselves and one another [10]. They are required for DISC assembly. Although the precise stochiometry of this complex remains partially unsolved, two independent studies have recently demonstrated that caspase-8 recruitment could lead to the formation of caspase-8 chains, representing up to nine-fold more caspase-8 than FADD [11,12]. Recruitment of these initiator caspases in a defined subcellular compartment within this scaffold is sufficient to induce their activation. An induced-proximity model was originally proposed in the late 1990’s to explain caspase-8 processing and activation following stimulation with another ligand of the TNF family, namely CD95L/Fas ligand [13,14]. Within the DISC, self-processing of caspase-8 or caspase-10, leads to the release of their active fragments to the cytosol. These fragments are composed of a large and a small catalytic subunit. Their assembly is sufficient to induce the cleavage and the activation of executioner caspases, including caspase-3 or caspase-7, leading to apoptosis (Figure 1).


Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL).

Elmallah MI, Micheau O - Mar Drugs (2015)

Schematic representation of apoptosis induced by TRAIL. Binding of TRAIL to its agonistic receptors (DR4 and/or DR5) leads to their oligomerization (1), and the subsequent recruitment of the cytosolic adapter protein FADD through DD homotypic interactions (2). FADD, in turn, enables recruitment of the initial pro-caspase-8/-10 through DED interactions leading to the formation of the so-called DISC (death-inducing signaling complex (3)). Within the DISC, chains of caspase-8/-10 are assembled (4), allowing self-processing of caspase-8/10 and release of their active fragments to the cytosol (5), where they activate, by proteolytic cleavage, effector caspases (6) to execute the apoptotic program (7). Amplification of the signal through the intrinsic pathway is sometimes required when caspase-8 is not sufficiently activated. In this scenario activation of mitochondria is induced by caspase-8/-10 through cleavage of the BH3-only Bcl-2 family protein Bid (8), whose truncated version (tBid) is able to translocate to mitochondria and induce a change of their outer membrane permeability, through Bak and Bax interactions (9), allowing cytochome c release, activation of caspase-9, another initiator caspase able to activate the executioner caspase-3/-7 (10).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4663558&req=5

marinedrugs-13-06884-f001: Schematic representation of apoptosis induced by TRAIL. Binding of TRAIL to its agonistic receptors (DR4 and/or DR5) leads to their oligomerization (1), and the subsequent recruitment of the cytosolic adapter protein FADD through DD homotypic interactions (2). FADD, in turn, enables recruitment of the initial pro-caspase-8/-10 through DED interactions leading to the formation of the so-called DISC (death-inducing signaling complex (3)). Within the DISC, chains of caspase-8/-10 are assembled (4), allowing self-processing of caspase-8/10 and release of their active fragments to the cytosol (5), where they activate, by proteolytic cleavage, effector caspases (6) to execute the apoptotic program (7). Amplification of the signal through the intrinsic pathway is sometimes required when caspase-8 is not sufficiently activated. In this scenario activation of mitochondria is induced by caspase-8/-10 through cleavage of the BH3-only Bcl-2 family protein Bid (8), whose truncated version (tBid) is able to translocate to mitochondria and induce a change of their outer membrane permeability, through Bak and Bax interactions (9), allowing cytochome c release, activation of caspase-9, another initiator caspase able to activate the executioner caspase-3/-7 (10).
Mentions: TRAIL agonist receptors contain an intracellular death domain (DD) that enables the assembly of the death-inducing signaling complex (DISC), leading eventually to apoptosis (Figure 1). Like most death ligands of the TNF superfamily, TRAIL binding to its cognate agonistic receptors triggers their aggregation, and with the exception of TNF-R1 [8], subsequent recruitment of the adaptor protein FADD (Fas Associated Death Domain) at the membrane level [9], through DD homotypic interactions (Figure 1). Once associated with TRAIL agonist receptors, FADD in turn enables the recruitment of the initiators caspases, namely caspase-8 and/or caspase-10, through its death effector domain (DED). DED-containing proteins, like proteins harboring DD’s, are able to interact with themselves and one another [10]. They are required for DISC assembly. Although the precise stochiometry of this complex remains partially unsolved, two independent studies have recently demonstrated that caspase-8 recruitment could lead to the formation of caspase-8 chains, representing up to nine-fold more caspase-8 than FADD [11,12]. Recruitment of these initiator caspases in a defined subcellular compartment within this scaffold is sufficient to induce their activation. An induced-proximity model was originally proposed in the late 1990’s to explain caspase-8 processing and activation following stimulation with another ligand of the TNF family, namely CD95L/Fas ligand [13,14]. Within the DISC, self-processing of caspase-8 or caspase-10, leads to the release of their active fragments to the cytosol. These fragments are composed of a large and a small catalytic subunit. Their assembly is sufficient to induce the cleavage and the activation of executioner caspases, including caspase-3 or caspase-7, leading to apoptosis (Figure 1).

Bottom Line: Marine biomass diversity is a tremendous source of potential anticancer compounds.Its selectivity for cancer cells has attracted much attention in oncology.This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Faculty of Science, Helwan University, Ain Helwan, Cairo 11790, Egypt. mohamed_almallah@science.helwan.edu.eg.

ABSTRACT
Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells has attracted much attention in oncology. This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells.

Show MeSH
Related in: MedlinePlus