Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2

Su, Bor Chyuan; Liu, Yi‐Chung; Ting, Chen-Hung; Lyu, Ping; Chen, Jyh-Yih

doi:10.3390/md18080417

Cited by 9 publications

(3 citation statements)

References 68 publications

(119 reference statements)

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“…TP4 was previously found to preferentially bind to mitochondria and the mitochondrial membrane protein, adenine nucleotide translocase 2, in non-small cell lung cancer cells and triple-negative breast cancer cells [25,39]. In the present study, we demonstrated that TP4 induces mitochondrial hyperpolarization in synovial sarcoma cells.…”

Section: Discussionsupporting

confidence: 68%

Marine Antimicrobial Peptide TP4 Exerts Anticancer Effects on Human Synovial Sarcoma Cells via Calcium Overload, Reactive Oxygen Species Production and Mitochondrial Hyperpolarization

Hung

et al. 2021

Marine Drugs

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Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1, and SOD-2. Moreover, TP4-induced mitochondrial hyperpolarization is followed by elevation of mitochondrial ROS. Calcium overload is also triggered by TP4, and cell death can be attenuated by a necrosis inhibitor, ROS scavenger or calcium chelator. In our experiments, TP4 displayed strong anticancer activity in human synovial sarcoma cells by disrupting oxidative status, promoting mitochondrial hyperpolarization and causing calcium overload.

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Section: Discussionsupporting

confidence: 68%

Marine Antimicrobial Peptide TP4 Exerts Anticancer Effects on Human Synovial Sarcoma Cells via Calcium Overload, Reactive Oxygen Species Production and Mitochondrial Hyperpolarization

Hung

et al. 2021

Marine Drugs

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“…On the one hand, the change in mitochondrial membrane potential will cause the abnormal continuous opening of the MPTP [ 38 ]. On the other hand, AMPs affect the opening of the MPTP by regulating the production of ROS, the concentration of Ca 2+ , or targeting the MPTP components [ 44 ]. Because MPTP spans the outer and inner membranes of mitochondria, it must also affect MOMP and MIMP [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability

Wang

Zhang

et al. 2022

IJMS

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Changes in mitochondrial membrane permeability are closely associated with mitochondria-mediated apoptosis. Antimicrobial peptides (AMPs), which have been found to enter cells to exert physiological effects, cause damage to the mitochondria. This paper reviews the molecular mechanisms of AMP-mediated apoptosis by changing the permeability of the mitochondrial membrane through three pathways: the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM), and mitochondrial permeability transition pore (MPTP). The roles of AMPs in inducing changes in membrane permeability and apoptosis are also discussed. Combined with recent research results, the possible application prospects of AMPs are proposed to provide a theoretical reference for the development of AMPs as therapeutic agents for human diseases.

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“…Ting et al [ 99 ] showed that O. niloticus ’s piscidin-4 peptide (TP4: FFRHLFRGAKAIFRGARQGXRAHKVVSRYRNRDVPETDNNQEEP [ 100 ]), endowed with a amphiphilic α-helical conformation structure and belonging to an antimicrobial peptide family first identified by Chinchar et al [ 101 ] in the mast cells of the hybrid striped bass ( Morone saxatilis × Morone chrysops ), exerted a microtubule-destabilizing activity, which could be the mechanistic requirement for the TP4-mediated death of A549 lung carcinoma cells. Additional studies have demonstrated that the peptide was also active on triple-negative breast cancer cells, glioblastoma cells and SW982 human synovial sarcoma cells [ 102 , 103 , 104 , 105 , 106 , 107 ]. The data reported for synovial tumor cells indicated the promotion of necrosis via the induction of calcium overload, mitochondrial hyperpolarization, ROS accumulation and impairment of the antioxidant defense.…”

Section: Marine Animals As Sources Of Anticancer Peptides: In Vitro E...mentioning

confidence: 99%

Natural Anticancer Peptides from Marine Animal Species: Evidence from In Vitro Cell Model Systems

Librizzi,

Martino,

Mauro

et al. 2023

Cancers

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Anticancer peptides are short and structurally heterogeneous aminoacidic chains, which display selective cytotoxicity mostly against tumor cells, but not healthy cells, based on their different cell surface properties. Their anti-tumoral activity is carried out through interference with intracellular homeostasis, such as plasmalemma integrity, cell cycle control, enzymatic activities and mitochondrial functions, ultimately acting as angiogenesis-, drug resistance- and metastasis-inhibiting agents, immune stimulators, differentiation inducers and necrosis or extrinsic/intrinsic apoptosis promoters. The marine environment features an ever-growing level of biodiversity, and seas and oceans are poorly exploited mines in terms of natural products of biomedical interest. Adaptation processes to extreme and competitive environmental conditions led marine species to produce unique metabolites as a chemical strategy to allow inter-individual signalization and ensure survival against predators, infectious agents or UV radiation. These natural metabolites have found broad use in various applications in healthcare management, due to their anticancer, anti-angiogenic, anti-inflammatory and regeneration abilities. The aim of this review is to pick selected studies that report on the isolation of marine animal-derived peptides and the identification of their anticancer activity in in vitro cultures of cancer cells, and list them with respect to the taxonomical hierarchy of the source organism.

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Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2

Cited by 9 publications

References 68 publications

Marine Antimicrobial Peptide TP4 Exerts Anticancer Effects on Human Synovial Sarcoma Cells via Calcium Overload, Reactive Oxygen Species Production and Mitochondrial Hyperpolarization

Marine Antimicrobial Peptide TP4 Exerts Anticancer Effects on Human Synovial Sarcoma Cells via Calcium Overload, Reactive Oxygen Species Production and Mitochondrial Hyperpolarization

Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability

Natural Anticancer Peptides from Marine Animal Species: Evidence from In Vitro Cell Model Systems

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