Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Sept. 12, 2022

Abstract Elesclomol is an anticancer drug that targets mitochondrial metabolism. In the past, elesclomol was recognized as inducer of oxidative stress, but now it has also been found to suppress cancer by inducing cuproptosis. Elesclomol’s activity determined dependence on The metabolism stem cells, cells resistant platinum drugs, proteasome inhibitors, molecularly targeted and with inhibited glycolysis significantly enhanced. exhibited tremendous toxicity all three kinds cells. Elesclomol's highly dependent its transport extracellular copper ions, a process involved in discovery cuproptosis perfected specific suppressor mechanism elesclomol. For some time, failed yield favorable results oncology clinical trials, safety application confirmed. Research progress relationship between elesclomol, provides possibility explore reapplication clinic. New trials should selectively target types high attempt combine platinum, or inhibitors. Herein, particular will be presented, which may shed light better tumor treatment.

Language: Английский

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Long non-coding RNA (lncRNA) H19 in human cancer: From proliferation and metastasis to therapy

Pharmacological Research, Journal Year: 2022, Volume and Issue: 184, P. 106418 - 106418

Published: Aug. 28, 2022

Language: Английский

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Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 150, P. 112963 - 112963

Published: April 22, 2022

Among the different kinds of tumors threatening human life, lung cancer is one that commonly observed in both males and females. The aggressive behavior interactions occurring tumor microenvironment enhances malignancy this tumor. cells have demonstrated capacity developing chemo- radio-resistance. LncRNAs are a category non-coding RNAs do not encode proteins, but their aberrant expression responsible for development, especially cancer. In present review, we focus on lncRNAs exosomal cancer, ability regulating proliferation metastasis. Cell cycle progression molecular mechanisms related to metastasis such as EMT MMPs regulated by lncRNAs. interact with miRNAs, STAT, Wnt, EZH2, PTEN PI3K/Akt signaling pathways affect cells. demonstrate tumor-suppressor tumor-promoting functions They can be considered biomarkers body fluids potential tools minimally invasive diagnosis. Furthermore, discuss regulation anti-cancer drugs genetic well role these factors therapy response

Language: Английский

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The two sides of chromosomal instability: drivers and brakes in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 29, 2024

Abstract Chromosomal instability (CIN) is a hallmark of cancer and associated with tumor cell malignancy. CIN triggers chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes chromosomes. arises errors DNA replication segregation during division, formation abnormal and/or structure Errors result licensing as well stress, such double-strand breaks stalled forks; meanwhile, stem defects machinery, centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, defective sister chromatids cohesion. In cells, deleterious damage, proteotoxic metabolic alteration, cycle arrest, senescence. Paradoxically, despite these negative consequences, one hallmarks found over 90% solid tumors blood cancers. Furthermore, could endow enhanced adaptation capabilities due increased intratumor heterogeneity, thereby facilitating adaptive resistance therapies; however, excessive induce death, “just-right” model for tumors. Elucidating complex nature crucial understanding dynamics tumorigenesis developing effective anti-tumor treatments. This review provides an overview causes consequences CIN, paradox phenomenon that continues perplex researchers. Finally, this explores potential CIN-based therapy.

Language: Английский

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Flavonoids and Gastric Cancer Therapy: From Signaling Pathway to Therapeutic Significance

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 3233 - 3253

Published: July 1, 2024

Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink other databases find the relevant literature last two decades. Using "gastric cancer", "stomach cancers", "flavonoid", "bioflavonoid", "2-Phenyl-Chromene" as keywords, were searched, then analyzed summarized mechanism flavonoids treatment GC. It was revealed that involves inhibiting growth, proliferation, invasion, metastasis, well inducing cell death through various processes such apoptosis, autophagy, ferroptosis, pyroptosis. Additionally, combining chemotherapeutic agents like 5-FU platinum can potentially reduce chemoresistance. Flavonoids also demonstrated enhanced activity when used combination products. Consequently, review proposes innovative perspectives for development anti-GC agents.

Language: Английский

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SRF/SLC31A1 signaling promotes cuproptosis induced by celastrol in NSCLC

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114165 - 114165

Published: Jan. 27, 2025

Language: Английский

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METTL3-mediated N6-methyladenosine modification and HDAC5/YY1 promote IFFO1 downregulation in tumor development and chemo-resistance

Cancer Letters, Journal Year: 2022, Volume and Issue: 553, P. 215971 - 215971

Published: Oct. 17, 2022

Language: Английский

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Heterometallic ruthenium–osmium complexes: dual photodynamic and photothermal therapy for melanoma and drug-resistant lung tumourin vivo

Inorganic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(15), P. 4552 - 4561

Published: Jan. 1, 2023

A hetero-dinuclear Ru–Os complex can entirely eradicate PDT-resistant melanoma and cisplatin-resistant non-small cell lung tumors by dual PDT/PTT under an 808 nm low-power laser. It also has low hepatorenal toxicity metal residue in mice.

Language: Английский

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The Application of 2d Mxene Nanosheet -Based Thermosensitive Gel Delivery System Loaded with Cisplatin and Imiquimod for Lung Cancer

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 4719 - 4733

Published: May 1, 2024

Introduction: Lung cancer's high incidence and dismal prognosis with traditional treatments like surgery radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded R837 cisplatin (DDP), encapsulated within hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), administered situ injections MDR@SHDS into tumor tissues combined photothermal therapy (PTT). The immune adjuvant enhances dendritic cell (DC) maturation phagocytosis, while PTT induces apoptosis necrosis by converting light energy heat energy. Methods: Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, thermography. In vitro experiments assessed Lewis proliferation using CCK-8, Edu, TUNEL assays. vivo on C57 mouse transplant tumors evaluated effect via thermography DC CD4+/CD8+ T ratios flow cytometry. anti-tumor efficacy was confirmed growth curve recording HE staining sections. Results: hydrogel exhibited excellent temperature sensitivity, controlled release properties, biocompatibility. revealed that had greater inhibitory compared to MDR@SHD alone. Combining immunotherapy, chemotherapy, yielded superior than individual treatments. Conclusion: MDR@SHDS, its simplicity, biocompatibility, enhanced combination PTT, presents promising therapeutic approach for treatment, offering potential clinical utility. Keywords: Mxene, delivery system, hydrogel,

Language: Английский

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Polyacetylenes from Codonopsis lanceolata Root Induced Apoptosis of Human Lung Adenocarcinoma Cells and Improved Lung Dysbiosis

BioMed Research International, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 15

Published: Feb. 18, 2022

Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer inflammation. However, anticancer substances in C. their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from water extracts polyacetylenes (CLP) then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, atractylenolide III. Treatment with CLP remarkably suppressed cell proliferation, colony formation, migration, invasion A549 cells. Synergistic effects lobetyolin lobetyol equivalent to antiproliferative activities CLP, while other did have any inhibition on viabilities also reduced expression Ras, PI3K, p-AKT, Bcl-2, cyclin D1, CDK4 but increased Bax, GSK-3β, clv-caspase-3, clv-caspase-9, which could be reversed by PI3K activator 740YP. Furthermore, retarded growths tumor pathogenic bacteria mice. It demonstrated that main antitumor lanceolata. induced apoptosis cells via inactivation Ras/PI3K/AKT pathway ameliorated dysbiosis, suggesting therapeutic potentials treating human cancer.

Language: Английский

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