Thioredoxin Signaling Pathways in Cancer

Antioxidants and Redox Signaling, Journal Year: 2022, Volume and Issue: unknown

Published: June 10, 2022

Significance: Thioredoxin (Trx) is a powerful antioxidant that reduces protein disulfides to maintain redox stability in cells and involved regulating multiple redox-dependent signaling pathways. Recent Advance: The current accumulation of findings suggests Trx participates pathways interact with various proteins manipulate their dynamic regulation structure function. These network are critical for cancer pathogenesis therapy. Promising clinical advances have been presented by most anticancer agents targeting such Critical Issues: We herein link the regulated system potential therapeutic opportunities, focusing on coordination strengths apoptosis, ferroptosis, immunomodulation, drug resistance. also provide mechanistic exploitation small molecules Future Directions: As research data accumulate, future complex networks Trx-related will gain detail. In-depth exploration establishment these pathways, including upstream downstream regulatory proteins, be advancing novel therapeutics. Antioxid. Redox Signal. 38, 403-424.

Language: Английский

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Recent advances in natural compounds inducing non-apoptotic cell death for anticancer drug resistance

Cancer Drug Resistance, Journal Year: 2023, Volume and Issue: 6(4), P. 709 - 27

Published: Oct. 16, 2023

The induction of cell death is recognized as a potent strategy for cancer treatment. Apoptosis an extensively studied form death, and multiple anticancer drugs exert their therapeutic effects by inducing it. Nonetheless, apoptosis evasion hallmark cancer, rendering cells resistant to chemotherapy drugs. Consequently, there growing interest in exploring novel non-apoptotic forms such ferroptosis, necroptosis, pyroptosis, paraptosis. Natural compounds with properties have garnered significant attention due advantages, including reduced risk drug resistance. Over the past two decades, numerous natural been discovered anti-resistance triggering these four mechanisms. This review primarily focuses on mechanisms recent advancements overcoming resistance Meanwhile, it highlights role effectively addressing through death.

Language: Английский

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Nanodrugs based on co-delivery strategies to combat cisplatin resistance

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 14 - 42

Published: April 17, 2024

Language: Английский

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α‐Hederin induces paraptosis by targeting GPCRs to activate Ca²⁺/MAPK signaling pathway in colorectal cancer

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(8)

Published: April 1, 2024

Abstract Background Non‐apoptotic cell death is presently emerging as a potential direction to overcome the apoptosis resistance of cancer cells. In current study, natural plant agent α‐hederin (α‐hed) induces caspase‐independent paraptotic modes death. Purpose The present study aimed investigate role α‐hed paraptosis and associated mechanism it. Methods proliferation was detected by CCK‐8. cytoplasm organelles were observed under electron microscope. Calcium (Ca 2+ ) level flow cytometry. Swiss Target Prediction tool analyzed molecule targets α‐hed. Molecular docking methods used evaluate binding abilities with targets. expressions genes proteins RT‐qPCR, western blotting, immunofluorescence, immunohistochemistry. Xenograft models in nude mice established anticancer effects vivo. Results exerted significant cytotoxicity against panel CRC lines inhibiting proliferation. Besides, it induced cytoplasmic vacuolation all Electron microscopy images showed aberrant dilation endoplasmic reticulum mitochondria. Both mRNA protein Alg‐2 interacting proteinX (Alix), marker paraptosis, inhibited both prediction molecular that structure could tightly target GPCRs. GPCRs reported activate phospholipase C (PLC)‐β3/ inositol 1,4,5‐trisphosphate receptor (IP3R)/ Ca / kinase alpha (PKCα) pathway, we then found PLCβ3, IP3R, PKCα increased After blocking GPCR signaling, not elevate less cytotoxicity. MAPK cascade symbol demonstrated activated elevating flux. Since non‐apoptotic chemo‐drug resistance, also 5‐fluorouracil‐resistant (5‐FU‐R) cells, reduced growth 5‐FU‐R xenografts. Conclusions Collectively, our findings proved promising candidate for inducing death, paraptosis. It may apoptotic‐based chemo‐resistance CRC.

Language: Английский

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Redox System and Oxidative Stress-Targeted Therapeutic Approaches in Bladder Cancer

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 287 - 287

Published: Feb. 26, 2024

Bladder cancer (BCa) is the most common genitourinary malignancy, with a high global incidence and recurrence rate that paired an increasing caregiver burden higher financial cost, in addition to morbidity mortality worldwide. Histologically, BCa categorized into non-muscle invasive, muscle metastatic BCa, on basis of which therapeutic strategy determined. Despite all innovations recent advances research, conventional therapies such as chemotherapy, immunotherapy, radiotherapy, surgery fall short complete management this important malignancy. Besides worrying trend, molecular development also remains poorly understood. Burgeoning evidence from experimental clinical studies suggests oxidative stress resulting imbalance between reactive oxygen species (ROS) generation body’s antioxidant production plays integral role progression. Hence, ROS-induced stress-related pathways are currently under investigation potential targets BCa. This review focuses our current understanding regarding ROS-associated pathogenesis progression, well antioxidants adjuvants therapy.

Language: Английский

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Dynamic metabolic change of cancer cells induced by natural killer cells at the single-cell level studied by label-free mass cytometry

Chemical Science, Journal Year: 2022, Volume and Issue: 13(6), P. 1641 - 1647

Published: Jan. 1, 2022

Label-free mass cytometry is utilized to study the dynamic metabolic change during apoptosis in HepG2 cells induced by NK92 MI at single-cell level. The heterogeneity of individual was revealed.

Language: Английский

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Discovery of Highly Potent Daphnane Diterpenoids Uncovers Importin-β1 as a Druggable Vulnerability in Castration-Resistant Prostate Cancer

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(38), P. 17522 - 17532

Published: Sept. 14, 2022

Importins are overexpressed in many cancers and mediate the abnormal nuclear transport of oncogenic factors. The druggable potential importins still remains unclear, largely because lack potent inhibitors. Herein, anti-castration-resistant prostate cancer (CRPC) screening a Euphorbiaceae diterpenoid library followed by target fishing led to identification highly importin-β1 inhibitor, daphnane DD1. DD1 selectively inhibited growth survival CRPC cells at subnanomolar concentrations completely blocked tumor preclinical models an extremely low dosage. Mechanistic studies revealed that targeting significantly reduced accumulation key drivers, shutting down their downstream signaling. Disruption predicted binding sites on abolished this anti-CRPC effect. These findings suggest is effective therapeutic as most inhibitor date can be developed therapeutics for treatment disease.

Language: Английский

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“Double-Edged Sword” Effect of Reactive Oxygen Species (ROS) in Tumor Development and Carcinogenesis

Physiological Research, Journal Year: 2023, Volume and Issue: 72(3)

Published: June 30, 2023

Reactive oxygen species (ROS) are small reactive molecules produced by cellular metabolism and regulate various physiological pathological functions. Many studies have shown that ROS plays an essential role in the proliferation inhibition of tumor cells. Different concentrations can a “double-edged sword” effect on occurrence development tumors. A certain concentration activate growth-promoting signals, enhance invasion cells, cause damage to biomacromolecules such as proteins nucleic acids. However, body's antitumor signal at higher levels initiating oxidative stress-induced apoptosis autophagy This review analyzes ROS's unique bidirectional regulation mechanism focusing key signaling pathways regulatory factors affect tumors providing ideas for in-depth understanding action its clinical application.

Language: Английский

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Nitrovin (difurazone), an antibacterial growth promoter, induces ROS-mediated paraptosis-like cell death by targeting thioredoxin reductase 1 (TrxR1)

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 210, P. 115487 - 115487

Published: March 7, 2023

Language: Английский

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A Mulberry Diels-Alder-Type Adduct, Kuwanon M, Triggers Apoptosis and Paraptosis of Lung Cancer Cells through Inducing Endoplasmic Reticulum Stress

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1015 - 1015

Published: Jan. 5, 2023

The mulberry tree (Morus alba) has been cultivated in China for thousands of years. Mulberry Diels-Alder-type adducts (MDAAs) are characteristic constituents the genus Morus. unique structure and diverse bioactivities MDAAs have attracted attention researchers. Kuwanon M (KWM) is an MDAA isolated from root bark Morus alba. This research reports growth inhibitory effects KWM on human lung cancer cells its possible mechanism. In A549 NCI-H292 cells, treatment induced suppression cell proliferation migration. appearance chromatin condensation, phosphatidyl serine exposure caspase cleavage indicated arising apoptosis. loss mitochondrial membrane potential (MMP), release cytochrome c dysregulation Bax/Bcl-2 demonstrated that KWM-induced apoptosis was through pathway. Paraptosis simultaneously detected under treatment, as evidenced by exhibition cytoplasmic vacuolation, down-regulation Alix up-regulation endoplasmic reticulum (ER) stress-related proteins. Mechanistically, ER stress activation unfolded protein response (UPR) pathways MAPK (JNK ERK) pathway, all which were critical paraptosis. These findings suggested possibility might be considered a therapeutic agent.

Language: Английский

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