Versatile function of NF-ĸB in inflammation and cancer DOI Creative Commons
Qiang Ma, Shuai Hao, Weilong Hong

et al.

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: July 16, 2024

Abstract Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, stemness. The function of NF-ĸB cancer progression response to chemotherapy has gained increasing attention. This review highlights the inflammation control, biological mechanisms, therapeutic implications treatment. is instrumental altering release inflammatory factors TNF-α, IL-6, IL-1β, which are key regulation carcinogenesis. Specifically, conditions including colitis, upregulation can intensify inflammation, potentially leading development colorectal cancer. Its pivotal extends regulating tumor microenvironment, impacting components macrophages, fibroblasts, T cells, natural killer cells. influences tumorigenesis dampen anti-tumor responses. Additionally, modulates death notably by inhibiting apoptosis ferroptosis. It also dual stimulating or suppressing autophagy cancers. Beyond these functions, controlling stem fostering angiogenesis, metastatic potential through EMT induction, reducing sensitivity radiotherapy. Given its oncogenic capabilities, research focused on products small molecule compounds that suppress NF-ĸB, offering promising avenues for therapy.

Language: Английский

Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD‐L1 for Enhanced Cancer Immunotherapy DOI
Boda Guo,

Feiya Yang,

Lingpu Zhang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(22)

Published: March 14, 2023

Cuproptosis is a new cell death that depends on copper (Cu) ionophores to transport Cu into cancer cells, which induces death. However, existing are small molecules with short blood half-life making it hard enough cells. Herein, reactive oxygen species (ROS)-sensitive polymer (PHPM) designed, used co-encapsulate elesclomol (ES) and form nanoparticles (NP@ESCu). After entering ES Cu, triggered by excessive intracellular ROS, readily released. work in concerted way not only kill cells cuproptosis, but also induce immune responses. In vitro, the ability of NP@ESCu efficiently cuproptosis investigated. addition, change transcriptomes treated explored RNA-Seq. vivo, found mice model subcutaneous bladder cancer, reprograming tumor microenvironment. Additionally, further combined anti-programmed protein ligand-1 antibody (αPD-L1). This study provides first report combining nanomedicine can αPD-L1 for enhanced therapy, thereby providing novel strategy future therapy.

Language: Английский

Citations

226
Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer DOI Creative Commons

Wei‐Kai Wang,

Kaizhong Lu, Xin Jiang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: June 6, 2023

Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, crosstalk between cuproptosis is obscure.We analyzed effect of inducers on copper ionophores-induced death through CCK-8 assay. was studied using immunofluorescence protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR western blot were adopted to explore machinery enhanced cuproptosis. And mouse xenograft model built detect synergy elesclomol-Cu sorafenib in vivo.Herein we found that erastin could enhance primary liver cancer cells by increasing dependent lipoylated aggregation. Mechanically, upregulated lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) degradation, reduced intracellular chelator glutathione (GSH) synthesis inhibiting cystine importing.Our findings proposed combination ionophores co-targeting be a novel therapeutic strategy for cancer.

Language: Английский

Citations

124
Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity DOI
Pascal Meier, Arnaud J. Legrand, Dieter Adam

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(5), P. 299 - 315

Published: March 7, 2024

Language: Английский

Citations

105
The pyroptotic role of Caspase-3/GSDME signalling pathway among various cancer: A Review DOI
Asif Ahmad Bhat, Riya Thapa, Obaid Afzal

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 242, P. 124832 - 124832

Published: May 15, 2023

Language: Английский

Citations

100
Deadly actin collapse by disulfidptosis DOI
Laura M. Machesky

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 375 - 376

Published: March 1, 2023

Language: Английский

Citations

98
4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to promote cuproptosis in colorectal cancer DOI Creative Commons
Wenchang Yang, Yaxin Wang,

Yongzhou Huang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 159, P. 114301 - 114301

Published: Jan. 25, 2023

Cuproptosis, a novel copper-induced cell death pathway, is linked to mitochondrial respiration and mediated by protein lipoylation. The discovery of cuproptosis unfolds new areas investigation, particularly in cancers. present study aimed explore the role colorectal cancer progression. genetic alterations colon were evaluated using database. MTT assays, colony formation, flow cytometry used examine effect elesclomol-Cu 4-Octyl itaconate (4-OI) on oxaliplatin-resistant viability. anti-tumor elesclomol with 4-OI was verified vivo assay. results showed that FDX1, SDHB, DLAT, DLST genes more highly expressed normal tissues than those primary tumor tissues. Patients high expressions these had better prognosis. Using assay formation analysis, pulse treatment significant inhibition viability HCT116, LoVo, HCT116-R cells. In addition, revealed significantly promoted apoptosis. Tetrathiomolybdate, copper chelator, markedly inhibited cuproptosis. Subsequently, we found 2-deoxy-D-glucose, glucose metabolism inhibitor, sensitized Furthermore, galactose further Interestingly, enhanced which irrelevant ROS production, apoptosis, necroptosis, or pyroptosis pathways. Aerobic glycolysis through GAPDH, one key enzymes glycolysis, sensitizing Meanwhile, FDX1 knockdown weakened ability promote experiments, effects. These indicated rapidly halted growth cells line. Importantly, aerobic targeting GAPDH

Language: Английский

Citations

85
Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors DOI Open Access

Luying Qiao,

Guo‐Qing Zhu, Tengfei Jiang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Language: Английский

Citations

83
Paraptosis: a unique cell death mode for targeting cancer DOI Creative Commons

Sweata Hanson,

Aiswarya Dharan,

P. V. Jinsha

et al.

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

Published: June 15, 2023

Programmed cell death (PCD) is the universal process that maintains cellular homeostasis and regulates all living systems' development, health disease. Out of all, apoptosis one major PCDs was found to play a crucial role in many disease conditions, including cancer. The cancer cells acquire ability escape apoptotic death, thereby increasing their resistance towards current therapies. This issue has led need search for alternate forms programmed mechanisms. Paraptosis an alternative pathway characterized by vacuolation damage endoplasmic reticulum mitochondria. Many natural compounds metallic complexes have been reported induce paraptosis lines. Since morphological biochemical features are much different from other PCDs, it understand modulators governing it. In this review, we highlighted factors trigger specific mediating pathway. Recent findings include inducing anti-tumour T-cell immunity immunogenic responses against A significant played also scaled its importance knowing mechanism. study xenograft mice, zebrafish model, 3D cultures, novel paraptosis-based prognostic model low-grade glioma patients broad aspect potential involvement field therapy. co-occurrence modes with photodynamic therapy combinatorial treatments tumour microenvironment summarized here. Finally, growth, challenges, future perspectives research discussed review. Understanding unique PCD would help develop combat chemo-resistance various

Language: Английский

Citations

57
Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy DOI Creative Commons
Xiaogang Zheng,

Xiaodong Jin,

Fei Ye

et al.

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: July 27, 2023

Abstract Background Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As novel modality that morphologically and mechanistically different from other forms of death, such as apoptosis necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on potential therapeutic strategy accumulated the rapid growth research targeting for tumor suppression in recent years. Methods We summarize currently known characteristics major regulatory mechanisms present role cellular stress responses, including ER autophagy. Furthermore, we elucidate applications radiotherapy immunotherapy, which will be beneficial exploring new strategies clinical treatment. Result conclusion Based specific biomarkers precise patient-specific assessment, great translated into practical approaches cancer therapy, significantly contributing prevention, diagnosis, prognosis, treatment cancer.

Language: Английский

Citations

48
Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy DOI Creative Commons
Youyou Li, Jing Liu, Yimei Chen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: March 13, 2024

Abstract The recent discovery of copper‐mediated and mitochondrion‐dependent cuproptosis has aroused strong interest in harnessing this novel mechanism cell death for cancer therapy. Here the design a core‐shell nanoparticle, CuP/Er, co‐delivery copper (Cu) erastin (Er) to cells synergistic ferroptosis is reported. anti‐Warburg effect Er sensitizes tumor Cu‐mediated cuproptosis, leading irreparable mitochondrial damage by depleting glutathione enhancing lipid peroxidation. CuP/Er induces immunogenic death, enhances antigen presentation, upregulates programmed death‐ligand 1 expression. Consequently, promotes proliferation infiltration T cells, when combined with immune checkpoint blockade, effectively reinvigorates mediate regression murine colon adenocarcinoma triple‐negative breast prevent metastasis. This study suggests unique opportunity synergize combination therapy nanoparticles elicit antitumor effects potentiate current immunotherapies.

Language: Английский

Citations

48