Alterperylenol as a Novel Thioredoxin Reductase Inhibitor Induces Liver Cancer Cell Apoptosis and Ferroptosis DOI
Junmin Xi, Lili Tian,

Jiahui Xi

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(50), P. 15763 - 15775

Published: Dec. 6, 2022

Natural products are a rich resource for discovering innovational drugs. Herein, we isolated and characterized two compounds dihydroalterperylenol (DAP) alterperylenol (AP) from Alternaria sp. MG1, an endophytic fungus Vitis quinquangularis, investigated the underlying antitumor mechanism of AP. Mechanistically, AP inhibits growth HepG2 cells by targeting selenoprotein thioredoxin reductase (TrxR) ultimately induces cell apoptosis ferroptosis. Compared to DAP, α,β-unsaturated carbonyl structure is indispensable moiety its activity TrxR inhibition. Specifically, inhibition causes extensive reactive oxygen species consequently results in DNA damage, G2/M cycle arrest, mitochondrial fission. Furthermore, ferroptosis driven via excess toxic lipid peroxidation elevation intracellular iron levels regulating iron-related proteins. In vivo validation also shows that owns anticancer xenograft mice. Collectively, our disclose novel natural inhibitor exerting effect inducing evidence promising candidate agent liver carcinoma therapy. The link further highlights physiological importance

Language: Английский

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy DOI Creative Commons
Zhuangzhuang Zheng, Jing Su, Xueying Bao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 4, 2023

Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS), leading to death tumor cells. OS not only apoptosis, autophagy ferroptosis, but also affects immune response. The combination RT immunotherapy has revolutionized management various cancers. In this process, caused by ROS plays a critical role. Specifically, RT-induced can promote release tumor-associated antigens (TAAs), regulate infiltration differentiation cells, manipulate expression checkpoints, change microenvironment (TME). review, we briefly summarize several ways in IR cell discuss interrelationship between antitumor immunity, with focus on interaction ferroptosis immunogenic death. We potential mechanisms regulates checkpoint expression, cells activity, differentiation. addition, conclude therapeutic opportunity improving radiotherapy regulating OS, may be beneficial clinical treatment.

Language: Английский

Citations

44
Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma DOI
Fuwei Li,

Zhenfan Wen,

Chuanxing Wu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(3), P. 1982 - 2003

Published: Jan. 23, 2024

Induction of immunogenic cell death (ICD) and activation the cyclic GMP-AMP synthase stimulator interferon gene (cGAS-STING) pathway are two potent anticancer immunotherapeutic strategies in hepatocellular carcinoma (HCC). Herein, 12 liver- mitochondria-targeting gold(I) complexes (

Language: Английский

Citations

23
Applications and Enhancement Strategies of ROS-based Non-invasive Therapies in Cancer Treatment DOI Creative Commons
Qiuyan Guo,

Yingnan Tang,

Shengmei Wang

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103515 - 103515

Published: Jan. 1, 2025

Language: Английский

Citations

2
Exogenous glycine promotes oxidation of glutathione and restores sensitivity of bacterial pathogens to serum-induced cell death DOI Creative Commons

Tian-shun Kou,

Jiahan Wu,

Xuan-wei Chen

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 58, P. 102512 - 102512

Published: Oct. 21, 2022

Pathogenic strains of bacteria are often highly adept at evading serum-induced cell death, which is an essential complement-mediated component the innate immune response. This phenomenon, known as serum-resistance, poorly understood, and a result, no effective clinical tools available to restore serum-sensitivity pathogenic bacteria. Here, we provide evidence that exogenous glycine reverses defects in glycine, serine threonine metabolism associated with serum resistance, restores susceptibility alters redox balance glutathione (GSH) metabolism. More specifically, Vibrio alginolyticus Escherichia coli, promotes oxidation GSH disulfide (GSSG), disrupts balance, increases oxidative stress reduces membrane integrity, leading increased binding complement. Antioxidant or ROS scavenging agents abrogate this effect generate potentiate stimulate serum-mediated death. Analysis several isolates E. coli demonstrates repressed serum-resistant These data suggest novel mechanism underlying serum-resistance bacteria, characterized by induced shift GSH/GSSG ratio impacting balance. The results could potentially lead approaches manage infections caused both aquaculture human health.

Language: Английский

Citations

49
Amplifying “eat me signal” by immunogenic cell death for potentiating cancer immunotherapy DOI

Yong Xi,

Lijie Chen,

Jian Tang

et al.

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 94 - 114

Published: Aug. 7, 2023

Immunogenic cell death (ICD) is a unique mode of death, which can release immunogenic damage-associated molecular patterns (DAMPs) and tumor-associated antigens to trigger long-term protective antitumor immune responses. Thus, amplifying "eat me signal" during tumor ICD cascade critical for cancer immunotherapy. Some therapies (radiotherapy, photodynamic therapy (PDT), photothermal (PTT), etc.) inducers (chemotherapeutic agents, have enabled initiate and/or facilitate activate Recently, nanostructure-based drug delivery systems been synthesized inducing through combining treatment chemotherapeutic photosensitizers PDT, transformation agents PTT, radiosensitizers radiotherapy, etc., loaded at an appropriate dosage in the designated place time, contributing higher efficiency lower toxicity. Also, immunotherapeutic combination with produce synergetic effects, thus potentiating Overall, our review outlines emerging inducers, nanostructure loading diverse evoke chemoradiotherapy, PTT or agents. Moreover, we discuss prospects challenges harnessing induction-based immunotherapy, highlight significance multidisciplinary interprofessional collaboration promote optimal translation this strategy.

Language: Английский

Citations

41
MCL attenuates atherosclerosis by suppressing macrophage ferroptosis via targeting KEAP1/NRF2 interaction DOI Creative Commons
Xing Luo, Yuehong Wang, Xinxin Zhu

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 69, P. 102987 - 102987

Published: Dec. 7, 2023

Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, effects and underlying mechanisms MCL on atherosclerosis are still unclear.

Language: Английский

Citations

38
Manganese-Enriched Zinc Peroxide Functional Nanoparticles for Potentiating Cancer Immunotherapy DOI
Mengli Zhou, Shuang Liang, Dan Liu

et al.

Nano Letters, Journal Year: 2023, Volume and Issue: 23(22), P. 10350 - 10359

Published: Nov. 6, 2023

Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy inducing immunogenic death (ICD) of cells activating stimulator interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tissue in situ generate •OH ICD effect. Moreover, Mn2+ activated STING synergistically induced secretion type I inflammatory cytokines specific T cell responses. Meanwhile, relieved immunosuppression TME through decreasing Tregs polarizing M2 macrophages M1 unleash a cascade adaptive response. In combination with anti-PD-1 antibody, showed superior inhibiting growth preventing lung metastasis. Our study demonstrates feasibility functional amplify innate stimulation, showing prominent strategy immunotherapy.

Language: Английский

Citations

33
Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution DOI
Lihua Luo, Sijie Wang, Yilong Hu

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(22), P. 22508 - 22526

Published: Nov. 10, 2023

Macrophages are central to the pathogenesis of kidney disease and serve as an effective therapeutic target for injury fibrosis. Among them, M2-type macrophages have double-edged effects regarding anti-inflammatory tissue repair. Depending on polarization M2 subtypes (M2a or M2c) in diseased microenvironment, they can either mediate normal repair drive In renal fibrosis, M2a promotes progression through macrophage-to-myofibroblast transition (MMT) cells, while M2c possesses potent functions repair, is inhibited. The mechanisms underlying this differentiation complex currently not well understood. Therefore, study, we first confirmed that M2a-derived MMT cells responsible development fibrosis demonstrated intensity TGF-β signaling a major factor determining differential M2c. Under excessive stimulation, undergoes process known whereas moderate stimulation favors phenotype macrophages. Based these findings, employed targeted nanotechnology codeliver endoplasmic reticulum stress (ERS) inhibitor (Ceapin 7, Cea C) conventional glucocorticoids (Dexamethasone, Dex D), precisely modulating ATF6/TGF-β/Smad3 axis within This approach calibrated level macrophages, promoting their toward suppressing polarization. study indicates combination ERS first-line drug holds promise resolution.

Language: Английский

Citations

29
Photodynamic Modulation of Endoplasmic Reticulum and Mitochondria Network Boosted Cancer Immunotherapy DOI Open Access
Xiaoli Wang,

Jieying Qian,

Zhenyu Yang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(4)

Published: Nov. 21, 2023

Abstract Immunogenic cell death (ICD) represents a promising approach for enhancing tumor therapy efficacy by inducing antitumor immune response. However, current ICD inducers often have insufficient endoplasmic reticulum (ER) enrichment and ineffectiveness in escape caused ER‐mitochondria interaction. In this study, kind of photoactivatable probe, THTTPy‐PTSA, which enables sequential targeting the ER mitochondria is developed. THTTPy‐PTSA incorporates p‐Toluenesulfonamide (PTSA) targeting, upon light irradiation, tetrahydropyridine group undergoes photo oxidative dehydrogenation reaction, transforming into pyridinium that acts as mitochondria‐targeting moiety. The results demonstrate exhibits exceptional subcellular translocation from to irradiation treatment, subsequently triggers stronger stress response through cascade‐amplification effect. Importantly, augmented leads substantial therapeutic 4T1 model eliciting release numerous damage‐associated molecular patterns, thereby evident widespread ICD, consequently efficacy. Collectively, findings emphasize pivotal role photodynamic modulation network, facilitated with precise spatial temporal regulation, effectively bolstering This innovative presents alternative addressing challenges associated cancer immunotherapy.

Language: Английский

Citations

28
Ultrasound targeted microbubble destruction-triggered nitric oxide release via nanoscale ultrasound contrast agent for sensitizing chemoimmunotherapy DOI Creative Commons
Yading Zhao, Dandan Shi, Lu Guo

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Jan. 30, 2023

Immunotherapy had demonstrated inspiring effects in tumor treatment, but only a minority of people could benefit owing to the hypoxic and immune-suppressed microenvironment (TME). Therefore, there was an urgent need for strategy that relieve hypoxia increase infiltration lymphocytes simultaneously. In this study, novel acidity-responsive nanoscale ultrasound contrast agent (L-Arg@PTX nanodroplets) constructed co-deliver paclitaxel (PTX) L-arginine (L-Arg) using homogenization/emulsification method. The L-Arg@PTX nanodroplets with uniform size about 300 nm high drug loading efficiency displayed good diagnostic imaging capability, improved aggregation achieved ultrasound-triggered release, which prevent premature leakage drugs thus improve biosafety. More critically, combination targeted microbubble destruction (UTMD) cellular reactive oxygen species (ROS), exerted oxidizing effect converted L-Arg into nitric oxide (NO), alleviating hypoxia, sensitizing chemotherapy increasing CD8 + cytotoxic T (CTLs) infiltration. Combined chemotherapeutic PTX-induced immunogenic cell death (ICD), promising enhance immunotherapy synergistically realize powerful treatment effect. Taken together, very hopeful vehicle integrated delivery, imaging, chemoimmunotherapy.

Language: Английский

Citations

26